Per O. Seglen
- Professor; PhD
Project description
Regulation of autophagic protein degradation, cytoskeletal organization and apoptotic cell death in normal and malignant rat liver cells
Normal tissues are continuously maintained and renewed by a balance between mass growth and autophagic degradation at the cellular level, and between cell division and apoptotic cell death at the tissue level. The uncontrolled growth of malignant tumours reflects the propensity of cancer cells to up-regulate mass growth and cell division as well as to down-regulate autophagy and apoptosis. Our project studies the molecular mechanisms involved in the regulation of the latter two processes, attempting to identify features that distinguish malignant cells from their normal counterparts.
Autophagy is a process by which cells, under conditions of stress or starvation, digest their own cytoplasm to obtain small molecules (like amino acids) needed for maintenance and renewal of essential cell functions. Specialized intracellular membrane cisternae, called phagophores, excise and enwrap pieces of cytoplasm, forming cytoplasm-filled vacuoles called autophagosomes. The autophagosomes subsequently fuse with endosomes (vacuoles that contain endocytosed material of extracellular origin) to form amphisomes, which eventually deliver their contents of cytoplasm and exogenous material to lysosomes (the digestive vacuoles of the cell) for degradation.
Our project has developed a method for purification of autophagosomes from isolated rat liver cells (Strømhaug et al. 1998, Biochem. J. 335, 217-224), and characterized these organelles biochemically as well as structurally (Fengsrud et al. 2000, Eur. J. Cell Biol. 79, 871-882). By the use of proteomics (protein separation by two-dimensional gel electrophoresis and column chromatography, combined with protein identification by mass spectrometry), we have been able to identify about 40 proteins that are selectively associated with autophagosomal membranes, including many novel enzyme forms (Fengsrud et al. 2000, Biochem. J. 352, 773-781). Several of these enzymes are functionally related, suggesting the participation of specific biochemical processes in the regulation of autophagic activity.
The use of proteomic methods has, furtermore, enabled our project to identify a signalling pathway that shuts down autophagy in liver cells during toxic stress. This pathway, which includes the AMP-activated protein kinase (AMPK), the stress-activated kinases SEK1 and JNK, and possibly S6-kinase (Ruud Larsen et al. 2002, J.Biol.Chem. 277, 34826-34835), also appears to regulate cytoskeletal organization and apoptotic cell death. Algal toxins like okadaic acid and microcystin induce a rapid activating phosphorylation of AMPK, and of cytoskeletal proteins like plectin and keratin, along with a disruption of the intracellular network of keratin intermediate filaments. This collapse of an important cytoskeletal element could well be a common cause of both the suppression of autophagy and of the apoptotic cell death that ensues several hours later.
A grapefuit flavonoid, naringin, prevents the AMPK phosphorylation, the keratin cytoskeletal collapse, the autophagy suppression and the apoptotic death elicited by algal toxins, probably reflecting an inhibitory effect of the flavonoid on an AMPK-activating protein kinase. Interestingly, naringin does not exert any such protective effect on liver cancer (hepatoma) cells of rat or human origin (Blankson et al. 2000, Cell Death Differ. 7, 739-746). The latter observation suggests the possibility of developing a novel type of cancer therapy, based on the use of a nonspecific cytotoxin (such as, e.g., okadaic acid) in combination with a specific cytoprotectant of normal cells (such as, e.g., naringin) to achieve a selective killing of cancer cells.
Publications 2021
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
Autophagy, 17 (1), 1-382
DOI 10.1080/15548627.2020.1797280, PubMed 33634751
Publications 2019
Measurement of Bulk Autophagy by a Cargo Sequestration Assay
Methods Mol Biol, 1880, 307-313
DOI 10.1007/978-1-4939-8873-0_20, PubMed 30610706
Publications 2016
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Autophagy, 12 (1), 1-222
DOI 10.1080/15548627.2015.1100356, PubMed 26799652
A Simple Cargo Sequestration Assay for Quantitative Measurement of Nonselective Autophagy in Cultured Cells
Methods Enzymol, 587, 351-364
DOI 10.1016/bs.mie.2016.09.064, PubMed 28253965
Publications 2015
Autophagy of cytoplasmic bulk cargo does not require LC3
Autophagy, 12 (2), 439-41
DOI 10.1080/15548627.2015.1076606, PubMed 26237084
Novel steps in the autophagic-lysosomal pathway
FEBS J, 282 (11), 2202-14
DOI 10.1111/febs.13268, PubMed 25779646
Macroautophagic cargo sequestration assays
Methods, 75, 25-36
DOI 10.1016/j.ymeth.2014.12.021, PubMed 25576638
Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs
Exp Cell Res, 333 (1), 21-38
DOI 10.1016/j.yexcr.2015.02.003, PubMed 25684710
Publications 2013
Modulation of intracellular calcium homeostasis blocks autophagosome formation
Autophagy, 9 (10), 1475-90
DOI 10.4161/auto.25900, PubMed 23970164
Autophagy proteins control goblet cell function by potentiating reactive oxygen species production
EMBO J, 32 (24), 3130-44
DOI 10.1038/emboj.2013.233, PubMed 24185898
Publications 2012
Guidelines for the use and interpretation of assays for monitoring autophagy
Autophagy, 8 (4), 445-544
DOI 10.4161/auto.19496, PubMed 22966490
Publications 2011
Seeing is believing: the impact of electron microscopy on autophagy research
Autophagy, 7 (9), 935-56
DOI 10.4161/auto.7.9.15760, PubMed 21566462
Autophagic activity measured in whole rat hepatocytes as the accumulation of a novel BHMT fragment (p10), generated in amphisomes by the asparaginyl proteinase, legumain
Autophagy, 7 (9), 1011-27
DOI 10.4161/auto.7.9.16436, PubMed 21610319
Publications 2010
The Norse god of autophagy. Interviewed by Daniel J Klionsky
Autophagy, 6 (8), 1017-31
DOI 10.4161/auto.6.8.13092, PubMed 20814236
Publications 2009
Sequestration assays for mammalian autophagy
Methods Enzymol, 452, 63-83
DOI 10.1016/S0076-6879(08)03605-7, PubMed 19200876
Phosphorylated and non-phosphorylated forms of catechol O-methyltransferase in rat liver, brain and other tissues
Biochem J, 417 (2), 535-45
DOI 10.1042/BJ20081284, PubMed 18831714
Publications 2008
Does bafilomycin A1 block the fusion of autophagosomes with lysosomes?
Autophagy, 4 (7), 849-50
DOI 10.4161/auto.6845, PubMed 18758232
Where endocytosis and autophagy meet: The amphisome
In Transworld Research Network (Fønhus MS, Mousavi SA, Berg T, eds.), Transworld Research Network, Trivandrum, India, 37/661, 61-100
PublikaID 37, ISBN 978-81-7895-364-9
Publications 2007
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Autophagy, 4 (2), 151-75
DOI 10.4161/auto.5338, PubMed 18188003
How shall I eat thee?
Autophagy, 3 (5), 413-6
DOI 10.4161/auto.4377, PubMed 17568180
Methods for monitoring autophagy from yeast to human
Autophagy, 3 (3), 181-206
DOI 10.4161/auto.3678, PubMed 17224625
Proteomic analysis of membrane-associated proteins from rat liver autophagosomes
Autophagy, 3 (4), 300-22
DOI 10.4161/auto.3910, PubMed 17377489
Publications 2006
Foreword
In Autophagy in Immunity and Infection (Deretic V, ed.), Wiley-VCH, Weinheim, XV-XVIII
PublikaID 38, ISBN 3-527-31450-4
Publications 2005
Pancreatic trypsin activates human promatrix metalloproteinase-2
J Mol Biol, 350 (4), 682-98
DOI 10.1016/j.jmb.2005.05.018, PubMed 15950241
Stimulation of hepatocytic AMP-activated protein kinase by okadaic acid and other autophagy-suppressive toxins
Biochem J, 386 (Pt 2), 237-44
DOI 10.1042/BJ20040609, PubMed 15461583
Comigration of two autophagosome-associated dehydrogenases on two-dimensional polyacrylamide gels
Autophagy, 1 (3), 157-62
DOI 10.4161/auto.1.3.2037, PubMed 16874067
Publications 2004
Toxin-induced tail phosphorylation of hepatocellular S6 kinase: evidence for a dual involvement of the AMP-activated protein kinase in S6 kinase regulation
Toxicol Sci, 82 (2), 628-37
DOI 10.1093/toxsci/kfh273, PubMed 15342961
Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway
Dev Cell, 7 (2), 179-92
DOI 10.1016/j.devcel.2004.07.005, PubMed 15296715
Publications 2003
Okadaic acid-induced, naringin-sensitive phosphorylation of glycine N-methyltransferase in isolated rat hepatocytes
Biochem J, 373 (Pt 2), 505-13
DOI 10.1042/BJ20030502, PubMed 12697024
Publications 2002
Naringin-sensitive phosphorylation of plectin, a cytoskeletal cross-linking protein, in isolated rat hepatocytes
J Biol Chem, 277 (38), 34826-35
DOI 10.1074/jbc.M205028200, PubMed 12095991
Publications 2001
Effects of the diarrhetic shellfish toxin, okadaic acid, on cytoskeletal elements, viability and functionality of rat liver and intestinal cells
Toxicon, 39 (2-3), 349-62
DOI 10.1016/s0041-0101(00)00137-9, PubMed 10978754
Effects of inhibitors of the vacuolar proton pump on hepatic heterophagy and autophagy
Biochim Biophys Acta, 1510 (1-2), 243-57
DOI 10.1016/s0005-2736(00)00354-0, PubMed 11342162
Evaluating biology: a scientometric study of a university biology department
In NIFU skriftserie, NIFU, Oslo, nr 6/2001, 70 s.
BIBSYS 010899006
Publications 2000
Prevention of toxin-induced cytoskeletal disruption and apoptotic liver cell death by the grapefruit flavonoid, naringin
Cell Death Differ, 7 (8), 739-46
DOI 10.1038/sj.cdd.4400705, PubMed 10918448
Ultrastructural characterization of the delimiting membranes of isolated autophagosomes and amphisomes by freeze-fracture electron microscopy
Eur J Cell Biol, 79 (12), 871-82
DOI 10.1078/0171-9335-00125, PubMed 11152279
Autophagosome-associated variant isoforms of cytosolic enzymes
Biochem J, 352 Pt 3 (Pt 3), 773-81
DOI 10.1042/0264-6021:3520773, PubMed 11104685
Publications 1998
Isolation and characterization of rat liver amphisomes. Evidence for fusion of autophagosomes with both early and late endosomes
J Biol Chem, 273 (34), 21883-92
DOI 10.1074/jbc.273.34.21883, PubMed 9705327
Inhibition of hepatocytic autophagy by adenosine, adenosine analogs and AMP
Biol Chem, 379 (11), 1341-7
DOI 10.1515/bchm.1998.379.11.1341, PubMed 9865607
Regional selective neuronal degeneration after protein phosphatase inhibition in hippocampal slice cultures: evidence for a MAP kinase-dependent mechanism
J Neurosci, 18 (18), 7296-305
DOI 10.1523/JNEUROSCI.18-18-07296.1998, PubMed 9736650
Inhibition of hepatocytic autophagy by adenosine, aminoimidazole-4-carboxamide riboside, and N6-mercaptopurine riboside. Evidence for involvement of amp-activated protein kinase
J Biol Chem, 273 (37), 23758-63
DOI 10.1074/jbc.273.37.23758, PubMed 9726984
Citation rates and journal impact factors are not suitable for evaluation of research
Acta Orthop Scand, 69 (3), 224-9
DOI 10.3109/17453679809000920, PubMed 9703393
Purification and characterization of autophagosomes from rat hepatocytes
Biochem J, 335 ( Pt 2) (Pt 2), 217-24
DOI 10.1042/bj3350217, PubMed 9761717
Publications 1997
Why the impact factor of journals should not be used for evaluating research
BMJ, 314 (7079), 498-502
DOI 10.1136/bmj.314.7079.497, PubMed 9056804
DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival
Cell Biol Toxicol, 13 (4-5), 301-15
DOI 10.1023/a:1007487425047, PubMed 9298250
Citations and journal impact factors: questionable indicators of research quality
Allergy, 52 (11), 1050-6
DOI 10.1111/j.1398-9995.1997.tb00175.x, PubMed 9404555
A novel method for the study of autophagy: destruction of hepatocytic lysosomes, but not autophagosomes, by the photosensitizing porphyrin tetra(4-sulphonatophenyl)porphine
Biochem J, 321 ( Pt 1) (Pt 1), 217-25
DOI 10.1042/bj3210217, PubMed 9003422
Differences between fluid-phase endocytosis (pinocytosis) and receptor-mediated endocytosis in isolated rat hepatocytes
Eur J Cell Biol, 73 (1), 28-39
PubMed 9174669
Publications 1996
Role of cAMP in the regulation of hepatocytic autophagy
Eur J Biochem, 236 (1), 163-70
DOI 10.1111/j.1432-1033.1996.00163.x, PubMed 8617261
Structural aspects of autophagy
Adv Exp Med Biol, 389, 103-11
DOI 10.1007/978-1-4613-0335-0_12, PubMed 8860999
Publications 1995
Disruption of the cytokeratin cytoskeleton and inhibition of hepatocytic autophagy by okadaic acid
Exp Cell Res, 218 (2), 522-30
DOI 10.1006/excr.1995.1187, PubMed 7540986
Ultrastructural and immunocytochemical characterization of autophagic vacuoles in isolated hepatocytes: effects of vinblastine and asparagine on vacuole distributions
Exp Cell Res, 221 (2), 504-19
DOI 10.1006/excr.1995.1402, PubMed 7493651
Vanadate inhibition of hepatocytic autophagy. Calcium-modulated and osmolality-modulated antagonism by asparagine
Eur J Biochem, 230 (1), 17-24
DOI 10.1111/j.1432-1033.1995.0017i.x, PubMed 7601097
Protection by naringin and some other flavonoids of hepatocytic autophagy and endocytosis against inhibition by okadaic acid
J Biol Chem, 270 (11), 5830-8
DOI 10.1074/jbc.270.11.5830, PubMed 7890712
Inhibition of asialoglycoprotein endocytosis and degradation in rat hepatocytes by protein phosphatase inhibitors
Biochem J, 311 ( Pt 1) (Pt 1), 317-26
DOI 10.1042/bj3110317, PubMed 7575471
Inhibition of autophagy and multiple steps in asialoglycoprotein endocytosis by inhibitors of tyrosine protein kinases (tyrphostins)
J Biol Chem, 270 (21), 12823-31
DOI 10.1074/jbc.270.21.12823, PubMed 7759538
Publications 1994
Separation of lysosomes and autophagosomes by means of glycyl-phenylalanine-naphthylamide, a lysosome-disrupting cathepsin-C substrate
Eur J Biochem, 221 (1), 595-602
DOI 10.1111/j.1432-1033.1994.tb18771.x, PubMed 8168547
[The impact factor as an instrument of allocation. Not accepted by the journals in Scandinavia]
Lakartidningen, 91 (8), 744-5
PubMed 8189977
Effect of 4-acetylaminofluorene and other tumour promoters on hepatocellular growth and binucleation
Carcinogenesis, 15 (2), 371-9
DOI 10.1093/carcin/15.2.371, PubMed 7508825
Flow cytometric investigation of a possible precursor--product relationship between oval cells and parenchymal cells in the rat liver
Carcinogenesis, 15 (1), 53-9
DOI 10.1093/carcin/15.1.53, PubMed 8293549
The fraction of cells in G1 with bound retinoblastoma protein increases with the duration of the cell cycle
Cell Prolif, 27 (2), 95-104
DOI 10.1111/j.1365-2184.1994.tb01408.x, PubMed 10465029
Ploidy-dependent growth and binucleation in cultured rat hepatocytes
Exp Cell Res, 214 (2), 551-60
DOI 10.1006/excr.1994.1293, PubMed 7925649
Proliferation of diploid hepatocytes and nonparenchymal (oval) cells during rat-liver regeneration in the presence of 2-acetylaminofluorene
Int J Oncol, 5 (4), 805-10
DOI 10.3892/ijo.5.4.805, PubMed 21559645
[How should the research be directed?]
Tidsskr Nor Laegeforen, 114 (25), 2970-2
PubMed 7974410
Publications 1993
Binucleation and polyploidization patterns in developmental and regenerative rat liver growth
Cell Prolif, 26 (6), 557-65
DOI 10.1111/j.1365-2184.1993.tb00033.x, PubMed 9116122
Dependence of hepatocytic autophagy on intracellularly sequestered calcium
J Biol Chem, 268 (35), 26107-12
PubMed 8253727
Inhibition of hepatocytic autophagy by okadaic acid and other protein phosphatase inhibitors
Eur J Biochem, 215 (1), 113-22
DOI 10.1111/j.1432-1033.1993.tb18013.x, PubMed 8393787
Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells
Carcinogenesis, 14 (12), 2501-5
DOI 10.1093/carcin/14.12.2501, PubMed 8269618
Evidence for acidity of prelysosomal autophagic/endocytic vacuoles (amphisomes)
Biochem J, 291 ( Pt 1) (Pt 1), 115-21
DOI 10.1042/bj2910115, PubMed 8471030
Publications 1992
Proteases and proteolysis in the lysosome
Experientia, 48 (2), 151-7
DOI 10.1007/BF01923508, PubMed 1740187
Reduced proliferative activity of polyploid cells in primary hepatocellular carcinoma
Carcinogenesis, 13 (10), 1795-801
DOI 10.1093/carcin/13.10.1795, PubMed 1330342
Analytical methods for the study of liver cell proliferation
Cytometry, 13 (4), 404-15
DOI 10.1002/cyto.990130411, PubMed 1382009
Prelysosomal and lysosomal connections between autophagy and endocytosis
Biochem J, 283 ( Pt 2) (Pt 2), 361-9
DOI 10.1042/bj2830361, PubMed 1575680
Protein kinase-dependent effects of okadaic acid on hepatocytic autophagy and cytoskeletal integrity
Biochem J, 284 ( Pt 3) (Pt 3), 633-6
DOI 10.1042/bj2840633, PubMed 1320371
Autophagy and other vacuolar protein degradation mechanisms
Experientia, 48 (2), 158-72
DOI 10.1007/BF01923509, PubMed 1740188
Publications 1991
Effects of adrenergic agonists and antagonists on autophagic activity in isolated rat liver cells
Biomed Biochim Acta, 50 (4-6), 383-7
PubMed 1801702
Role of cyclic nucleotides in the control of hepatic autophagy
Biomed Biochim Acta, 50 (4-6), 389-92
PubMed 1666282
Inhibition of autophagic-lysosomal delivery and autophagic lactolysis by asparagine
J Cell Biol, 113 (6), 1305-12
DOI 10.1083/jcb.113.6.1305, PubMed 1904444
Diploid growth pattern of hepatocellular tumours induced by various carcinogenic treatments
Carcinogenesis, 12 (2), 325-7
DOI 10.1093/carcin/12.2.325, PubMed 1847321
Citation frequency and journal impact: valid indicators of scientific quality?
J Intern Med, 229 (2), 109-11
DOI 10.1111/j.1365-2796.1991.tb00316.x, PubMed 1997634
Hepatocytic autophagy
Biomed Biochim Acta, 50 (4-6), 373-81
PubMed 1666281
Publications 1990
Effects of the tumor promoter 2-acetylaminofluorene and of 4-acetylaminofluorene on rat liver growth
Bull Cancer, 77 (5), 461-6
PubMed 2400817
Both endocytic and endogenous protein degradation in fibroblasts is stimulated by serum/amino acid deprivation and inhibited by 3-methyladenine
Biochem J, 272 (3), 577-81
DOI 10.1042/bj2720577, PubMed 1702625
Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes
J Cell Biol, 111 (3), 941-53
DOI 10.1083/jcb.111.3.941, PubMed 2391370
Studies on the mitoinhibitory effect of orotic acid on hepatocytes in primary culture
Carcinogenesis, 11 (6), 981-4
DOI 10.1093/carcin/11.6.981, PubMed 2347072
Cell biology of hepatocarcinogenesis
Crit Rev Oncog, 1 (4), 437-66
PubMed 1964598
Growth-related alterations during liver carcinogenesis: effect of promoters
Environ Health Perspect, 88, 197-205
DOI 10.1289/ehp.9088197, PubMed 2272315
Non-selective autophagy
Semin Cell Biol, 1 (6), 441-8
PubMed 2103895
Liver tumor promoters stimulate growth of transplanted hepatocellular carcinomas
Hepatology, 12 (2), 295-300
DOI 10.1002/hep.1840120217, PubMed 2167869
Publications 1989
Experimental characterization of the autophagic-lysosomal pathway in isolated rat hepatocytes
Biochem Soc Symp, 55, 129-43
PubMed 2619764
Energy dependence of different steps in the autophagic-lysosomal pathway
J Biol Chem, 264 (12), 6699-704
PubMed 2708336
Diploid nature of hepatocellular tumours developing from transplanted preneoplastic liver cells
Br J Cancer, 59 (2), 198-205
DOI 10.1038/bjc.1989.41, PubMed 2930686
[Evaluation of scientific quality using citation analysis and other bibliometric methods]
Nord Med, 104 (12), 331-5, 341
PubMed 2594499
[Use of citation analysis and other bibliometric methods in evaluation of the quality of research]
Tidsskr Nor Laegeforen, 109 (31), 3229-4
PubMed 2595690
From bad to worse: evaluation by Journal Impact
Trends Biochem Sci, 14 (8), 326-7
DOI 10.1016/0968-0004(89)90163-1, PubMed 2799903
Neuroendocrine dysdifferentiation and bombesin production in carcinogen-induced hepatocellular rat tumours
Carcinogenesis, 10 (1), 21-5
DOI 10.1093/carcin/10.1.21, PubMed 2910524
Publications 1988
Prelysosomal convergence of autophagic and endocytic pathways
Biochem Biophys Res Commun, 151 (1), 40-7
DOI 10.1016/0006-291x(88)90556-6, PubMed 3126737
Changes in ploidy distributions in human liver carcinogenesis
J Natl Cancer Inst, 80 (18), 1480-5
DOI 10.1093/jnci/80.18.1480, PubMed 2846856
The polyploidizing growth pattern of normal rat liver is replaced by divisional, diploid growth in hepatocellular nodules and carcinomas
Carcinogenesis, 9 (6), 939-45
DOI 10.1093/carcin/9.6.939, PubMed 3370757
2-Acetylaminofluorene promotion of liver carcinogenesis by a non-cytotoxic mechanism
Carcinogenesis, 9 (4), 581-7
DOI 10.1093/carcin/9.4.581, PubMed 2895691
Publications 1987
Sugar uptake by fluid-phase pinocytosis and diffusion in isolated rat hepatocytes
Biochem J, 243 (3), 655-60
DOI 10.1042/bj2430655, PubMed 3663095
Temperature dependence of protein degradation, autophagic sequestration and mitochondrial sugar uptake in rat hepatocytes
Biochim Biophys Acta, 929 (2), 128-33
DOI 10.1016/0167-4889(87)90167-4, PubMed 3593777
Energy dependence of autophagic protein degradation in isolated rat hepatocytes
Eur J Biochem, 164 (1), 197-203
DOI 10.1111/j.1432-1033.1987.tb11011.x, PubMed 3830181
Transplantation of preneoplastic rat hepatocytes by intraportal injection
Toxicol Pathol, 15 (1), 78-81
DOI 10.1177/019262338701500110, PubMed 3554470
Endocytosis of asialo-glycoproteins and attachment to asialo-glycoproteins of hepatocytes from carcinogen-treated rats
Toxicol Pathol, 15 (1), 88-92
DOI 10.1177/019262338701500112, PubMed 3576077
Publications 1986
Use of electrical methods in the study of hepatocytic autophagy
Biomed Biochim Acta, 45 (11-12), 1635-45
PubMed 3579882
Use of a hydrolysable probe, [14C]lactose, to distinguish between pre-lysosomal and lysosomal steps in the autophagic pathway
Exp Cell Res, 166 (1), 1-14
DOI 10.1016/0014-4827(86)90503-3, PubMed 3743649
Increase in cis-dichlorodiammineplatinum (II) cytotoxicity upon reversible electropermeabilization of the plasma membrane in cultured human NHIK 3025 cells
Eur J Cancer Clin Oncol, 22 (12), 1523-30
DOI 10.1016/0277-5379(86)90090-8, PubMed 3595677
Characterization of hepatocytes from carcinogen-treated rats by two-parametric flow cytometry
Carcinogenesis, 7 (1), 171-3
DOI 10.1093/carcin/7.1.171, PubMed 3943139
Isolation of carcinogen-induced diploid rat hepatocytes by centrifugal elutriation
Cancer Res, 46 (9), 4732-7
PubMed 2873888
Radiolabelled sugars as probes of hepatocytic autophagy
Biomed Biochim Acta, 45 (11-12), 1647-56
PubMed 3579883
Use of [3H]raffinose as a specific probe of autophagic sequestration
Exp Cell Res, 162 (1), 273-7
DOI 10.1016/0014-4827(86)90446-5, PubMed 3940229
Changes in cellular ploidy and autophagic responsiveness during rat liver carcinogenesis
Toxicol Pathol, 14 (3), 342-8
DOI 10.1177/019262338601400309, PubMed 3787117
Publications 1985
Sequestration and hydrolysis of electroinjected [14C]lactose as a means of investigating autophagosome-lysosome fusion in isolated rat hepatocytes
Prog Clin Biol Res, 180, 475-7
PubMed 4034554
Autophagic sequestration of [14C]sucrose introduced into isolated rat hepatocytes by electrical and non-electrical methods
Exp Cell Res, 160 (2), 449-58
DOI 10.1016/0014-4827(85)90192-2, PubMed 4043252
Use of digitonin extraction to distinguish between autophagic-lysosomal sequestration and mitochondrial uptake of [14C]sucrose in hepatocytes
Biochem J, 232 (3), 773-80
DOI 10.1042/bj2320773, PubMed 4091820
Cell cycle traverse and protein metabolism in human NHIK 3025 cells: the role of anchorage
J Cell Physiol, 125 (3), 528-32
DOI 10.1002/jcp.1041250324, PubMed 4066771
Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats
Exp Cell Res, 157 (1), 15-28
DOI 10.1016/0014-4827(85)90148-x, PubMed 2857648
Pathways of intracellular sequestration and protein degradation in isolated rat hepatocytes
Prog Clin Biol Res, 180, 437-46
PubMed 4034550
Autophagy and protein degradation in isolated rat hepatocytes
Biochem Soc Trans, 13 (6), 1007-10
DOI 10.1042/bst0131007, PubMed 4092819
Conversion of dense lysosomes into light lysosomes during hepatocytic autophagy
Exp Cell Res, 157 (2), 550-5
DOI 10.1016/0014-4827(85)90141-7, PubMed 3979450
Autophagic-lysosomal and mitochondrial sequestration of [14C]sucrose. Density gradient distribution of sequestered radioactivity
Eur J Biochem, 153 (2), 223-9
DOI 10.1111/j.1432-1033.1985.tb09290.x, PubMed 4076173
Publications 1984
Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis
Carcinogenesis, 5 (10), 1267-75
DOI 10.1093/carcin/5.10.1267, PubMed 6149024
Amino acid control of autophagic sequestration and protein degradation in isolated rat hepatocytes
J Cell Biol, 99 (2), 435-44
DOI 10.1083/jcb.99.2.435, PubMed 6746735
Amino acid control of protein degradation in normal and leukemic human lymphocytes
Exp Cell Res, 155 (1), 121-8
DOI 10.1016/0014-4827(84)90773-0, PubMed 6489454
Trapping of electro-injected [14C]sucrose by hepatocyte mitochondria: a mechanism for cellular autofiltration?
Biochem Biophys Res Commun, 119 (3), 955-61
DOI 10.1016/0006-291x(84)90866-0, PubMed 6712679
Publications 1983
Paradoxical stimulation by amino acids of the degradation of [35S]methionine-labelled, short-lived protein in isolated rat hepatocytes
Biochem Biophys Res Commun, 117 (2), 509-16
DOI 10.1016/0006-291x(83)91229-9, PubMed 6661239
Inhibitors of lysosomal function
Methods Enzymol, 96, 737-64
DOI 10.1016/s0076-6879(83)96063-9, PubMed 6361463
Structural and physical changes in lysosomes from isolated rat hepatocytes treated with methylamine
Biochim Biophys Acta, 763 (3), 284-91
DOI 10.1016/0167-4889(83)90136-2, PubMed 6626583
Cellular and lysosomal uptake of methylamine in isolated rat hepatocytes
Biochem J, 210 (3), 929-36
DOI 10.1042/bj2100929, PubMed 6870811
Publications 1982
6-substituted purines: a novel class of inhibitors of endogenous protein degradation in isolated rat hepatocytes
Arch Biochem Biophys, 217 (1), 282-94
DOI 10.1016/0003-9861(82)90504-5, PubMed 6889839
Autophagic sequestration of [14C]sucrose, introduced into rat hepatocytes by reversible electro-permeabilization
Exp Cell Res, 142 (1), 1-14
DOI 10.1016/0014-4827(82)90402-5, PubMed 7140848
Accumulation of autophagosomes after inhibition of hepatocytic protein degradation by vinblastine, leupeptin or a lysosomotropic amine
Exp Cell Res, 137 (1), 191-201
DOI 10.1016/0014-4827(82)90020-9, PubMed 7056284
Inhibition of hepatocytic protein degradation by inducers of autophagosome accumulation
Acta Biol Med Ger, 41 (1), 125-30
PubMed 7113543
The relation between protein accumulation and cell cycle traverse of human NHIK 3025 cells in unbalanced growth
J Cell Physiol, 112 (1), 19-26
DOI 10.1002/jcp.1041120105, PubMed 7107714
Amino acid and energy requirements for rat hepatocytes in primary culture
In Vitro, 18 (1), 43-54
DOI 10.1007/BF02796384, PubMed 6763597
3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes
Proc Natl Acad Sci U S A, 79 (6), 1889-92
DOI 10.1073/pnas.79.6.1889, PubMed 6952238
Publications 1981
Role of microtubuli in the lysosomal degradation of endogenous and exogenous protein in isolated rat hepatocytes
Hoppe Seylers Z Physiol Chem, 362 (5), 549-56
DOI 10.1515/bchm2.1981.362.1.549, PubMed 6166527
Effects of amino acids and amino acid analogues on lysosomal protein degradation in isolated rat hepatocytes
Acta Biol Med Ger, 40 (10-11), 1603-12
PubMed 6177140
Leucine inhibition of autophagic vacuole formation in isolated rat hepatocytes
Exp Cell Res, 134 (1), 33-9
DOI 10.1016/0014-4827(81)90460-2, PubMed 7250217
Effects of amino acid analogues on protein degradation in isolated rat hepatocytes
Biochim Biophys Acta, 676 (1), 43-50
DOI 10.1016/0304-4165(81)90007-6, PubMed 7260111
Inhibition of autophagic vacuole formation and protein degradation by amino acids in isolated hepatocytes
Exp Cell Res, 133 (2), 431-6
DOI 10.1016/0014-4827(81)90336-0, PubMed 7238609
Inhibition of autophagic sequestration and endogenous protein degradation in isolated rat hepatocytes by methylated adenosine derivatives
FEBS Lett, 134 (2), 194-6
DOI 10.1016/0014-5793(81)80600-x, PubMed 7308488
Inhibition of hepatocytic protein degradation by methylaminopurines and inhibitors of protein synthesis
Biochim Biophys Acta, 676 (2), 213-20
DOI 10.1016/0304-4165(81)90189-6, PubMed 7260116
Effects of insulin and anchorage on hepatocytic protein metabolism and amino acid transport
J Cell Sci, 48, 1-18
DOI 10.1242/jcs.48.1.1, PubMed 7024288
Effect of serum step-down on protein metabolism and proliferation kinetics of NHIK 3025 cells
J Cell Physiol, 107 (1), 47-57
DOI 10.1002/jcp.1041070107, PubMed 7194351
The role of protein accumulation in the cell cycle control of human NHIK 3025 cells
J Cell Physiol, 109 (3), 411-8
DOI 10.1002/jcp.1041090306, PubMed 7320058
Effects of antibiotics on protein synthesis and degradation in primary cultures of rat hepatocytes
In Vitro, 17 (1), 71-6
DOI 10.1007/BF02618033, PubMed 7216241
Vanadate inhibits protein degradation in isolated rat hepatocytes
J Biol Chem, 256 (15), 7699-701
PubMed 6167567
Inhibitors and pathways of hepatocytic protein degradation
Acta Biol Med Ger, 40 (10-11), 1587-98
PubMed 7342604
Publications 1980
Adsorption, simple binding and complex binding of rat hepatocytes to various in vitro substrata
Exp Cell Res, 129 (1), 239-49
DOI 10.1016/0014-4827(80)90347-x, PubMed 6159218
Differential effects of proteinase inhibitors and amines on the lysosomal and non-lysosomal pathways of protein degradation in isolated rat hepatocytes
Biochim Biophys Acta, 632 (1), 73-86
DOI 10.1016/0304-4165(80)90250-0, PubMed 7417519
Protein metabolism and survival of rat hepatocytes in early culture
Exp Cell Res, 130 (1), 185-90
DOI 10.1016/0014-4827(80)90055-5, PubMed 6161016
Effects of lysosomotropic monoamines, diamines, amino alcohols, and other amino compounds on protein degradation and protein synthesis in isolated rat hepatocytes
Mol Pharmacol, 18 (3), 468-75
PubMed 7464813
Amino acid inhibition of the autophagic/lysosomal pathway of protein degradation in isolated rat hepatocytes
Biochim Biophys Acta, 630 (1), 103-18
DOI 10.1016/0304-4165(80)90141-5, PubMed 7388042
Amino acid control of protein synthesis and degradation in isolated rat hepatocytes
Ann N Y Acad Sci, 349, 1-17
DOI 10.1111/j.1749-6632.1980.tb29510.x, PubMed 6939359
Subcellular distribution of proteolytically generated valine in isolated rat hepatocytes
Eur J Biochem, 107 (2), 587-96
DOI 10.1111/j.1432-1033.1980.tb06067.x, PubMed 7398655
Publications 1979
Protein synthesis and protein degradation through the cell cycle of human NHIK 3025 cells in vitro
Exp Cell Res, 123 (1), 63-72
DOI 10.1016/0014-4827(79)90421-x, PubMed 488184
Hepatocyte suspensions and cultures as tools in experimental carcinogenesis
J Toxicol Environ Health, 5 (2-3), 551-60
DOI 10.1080/15287397909529766, PubMed 224209
Inhibition of cell spreading by lysosomotropic amines
FEBS Lett, 105 (2), 345-8
DOI 10.1016/0014-5793(79)80645-6, PubMed 488362
Inhibition of the lysosomal pathway of protein degradation in isolated rat hepatocytes by ammonia, methylamine, chloroquine and leupeptin
Eur J Biochem, 95 (2), 215-25
DOI 10.1111/j.1432-1033.1979.tb12956.x, PubMed 456353
Publications 1978
Effects of amino acids, ammonia and leupeptin on protein synthesis and degradation in isolated rat hepatocytes
Biochem J, 174 (2), 469-74
DOI 10.1042/bj1740469, PubMed 708399
Attachment of rat hepatocytes in vitro to substrata of serum protein, collagen, or concanavalin A
Exp Cell Res, 116 (1), 199-206
DOI 10.1016/0014-4827(78)90076-9, PubMed 29767
Effect of temperature and divalent cations on the substratum attachment of rat hepatocytes in vitro
J Cell Sci, 34, 117-31
DOI 10.1242/jcs.34.1.117, PubMed 748333
Valine uptake and incorporation into protein in isolated rat hepatocytes. Nature of the precursor pool for protein synthesis
Eur J Biochem, 85 (1), 15-25
DOI 10.1111/j.1432-1033.1978.tb12208.x, PubMed 639812
Effects of aminooxyacetate, alanine and other amino acids on protein synthesis in isolated rat hepatocytes
Biochim Biophys Acta, 520 (3), 630-41
DOI 10.1016/0005-2787(78)90148-x, PubMed 718918
Publications 1977
Inhibitor of protein degradation formed during incubation of isolated rat hepatocytes in a cell culture medium. Its identification as ammonia
Exp Cell Res, 107 (1), 207-17
DOI 10.1016/0014-4827(77)90402-5, PubMed 16760
Protein-catabolic stage of isolated rat hepatocytes
Biochim Biophys Acta, 496 (1), 182-91
DOI 10.1016/0304-4165(77)90126-x, PubMed 836893
Ammonia inhibits protein secretion in isolated rat hepatocytes
Biochim Biophys Acta, 496 (1), 29-35
DOI 10.1016/0304-4165(77)90112-x, PubMed 836896
Protein degradation in isolated rat hepatocytes
Acta Biol Med Ger, 36 (11-12), 1789-804
PubMed 616724
Publications 1976
[Ammonia inhibition of protein degradation in isolated rat hepatocytes: quantitative alterations in the lysosomal system (author's transl)]
Verh Dtsch Ges Pathol, 223-6
PubMed 1035828
Preparation of isolated rat liver cells
Methods Cell Biol, 13, 29-83
DOI 10.1016/s0091-679x(08)61797-5, PubMed 177845
Incorporation of radioactive amino acids into protein in isolated rat hepatocytes
Biochim Biophys Acta, 442 (3), 391-404
DOI 10.1016/0005-2787(76)90313-0, PubMed 963056
Ammonia inhibition of protein degradation in isolated rat hepatocytes. Quantitative ultrastructural alterations in the lysosomal system
Exp Cell Res, 100 (2), 276-80
DOI 10.1016/0014-4827(76)90148-8, PubMed 939253
Publications 1975
Mass isolation and culture of rat kupffer cells
J Exp Med, 141 (1), 1-10
DOI 10.1084/jem.141.1.1, PubMed 1090696
[The university's odontological collection]
Nor Tannlaegeforen Tid, 85 (6), 236-40
PubMed 1094410
Protein degradation in isolated rat hepatocytes is inhibited by ammonia
Biochem Biophys Res Commun, 66 (1), 44-52
DOI 10.1016/s0006-291x(75)80292-0, PubMed 1164434
Publications 1974
The use of Metrizamide as a gradient medium for isopycnic separation of rat liver cells
FEBS Lett, 43 (3), 252-6
DOI 10.1016/0014-5793(74)80654-x, PubMed 4416578
Proceedings: Carbohydrate metabolism of isolated parenchymal rat liver cells
Hoppe Seylers Z Physiol Chem, 355 (10), 1255
PubMed 4461596
[The pelican]
Tid Tann, 35 (2), 92-7
PubMed 4527569
Control of glycogen metabolism in isolated rat liver cells by glucose, insulin and glucagon
Acta Endocrinol Suppl (Copenh), 191, 153-8
DOI 10.1530/acta.0.077s0153, PubMed 4548796
Differones: Control of gene expression and cellular differentiation by hormones and other agents, with particular emphasis on liver tissue
Universitetsforl., Oslo, [1] bl., 131 s.
BIBSYS 011869836
Hormonal control of gene expression
Norsk Hydro's institutt for kreftforskning, Oslo, Bl.359 s.+13 særtr.
BIBSYS 930873009
Publications 1973
Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion
Exp Cell Res, 82 (2), 391-8
DOI 10.1016/0014-4827(73)90357-1, PubMed 4358115
Preparation of rat liver cells. II. Effects of ions and chelators on tissue dispersion
Exp Cell Res, 76 (1), 25-30
DOI 10.1016/0014-4827(73)90414-x, PubMed 4630105
Effects of anaerobiosis, glucose, insulin and glucagon on glycogen metabolism in isolated parenchymal rat liver cells
FEBS Lett, 36 (3), 309-12
DOI 10.1016/0014-5793(73)80398-9, PubMed 4763310
Glycogen synthesis in isolated parenchymal rat liver cells
FEBS Lett, 30 (1), 25-28
DOI 10.1016/0014-5793(73)80611-8, PubMed 11947054
Publications 1972
Induction of tryptophan oxygenase in primary rat liver cell suspensions by glucocorticoid hormone
Exp Cell Res, 72 (2), 571-4
DOI 10.1016/0014-4827(72)90034-1, PubMed 5037935
Enrichment of glucagon sensitive adenyl cyclase upon preparation of parenchymal cells from rat liver
Arch Biochem Biophys, 150 (2), 807-9
DOI 10.1016/0003-9861(72)90102-6, PubMed 5044053
An effect of ethanol administration on tryptophan oxygenase in the perfused rat liver. Decreased enzyme synthesis dependent on low perfusate pH
Biochem Pharmacol, 21 (13), 1849-59
DOI 10.1016/0006-2952(72)90181-5, PubMed 4405195
Preparation of rat liver cells. I. Effect of Ca 2+ on enzymatic dispersion of isolated, perfused liver
Exp Cell Res, 74 (2), 450-4
DOI 10.1016/0014-4827(72)90400-4, PubMed 4343020
The effect of perfusate pH on respiration and glycolysis in the isolated rat liver perfused with an erythrocyte- and protein-free medium
Biochim Biophys Acta, 264 (3), 398-410
DOI 10.1016/0304-4165(72)90002-5, PubMed 5027624
Publications 1971
Insulin and amino-acid regulation of polysomes in perfused, diabetic rat liver
Nat New Biol, 229 (8), 244-5
DOI 10.1038/newbio229244a0, PubMed 5279798
Regulation of tyrosine transaminase degradation in the isolated perfused rat liver by cycloheximide and insulin
Biochim Biophys Acta, 230 (2), 319-26
DOI 10.1016/0304-4165(71)90218-2, PubMed 4396768
[Extraction devices]
Tid Tann, 32 (5), 273-9
PubMed 5292780
[Dental extraction forceps]
Tid Tann, 32, 273-9
PubMed 11633374
Publications 1970
An effect of glucocorticoid hormone on the nuclear ribonucleoprotein of rat liver
Hoppe Seylers Z Physiol Chem, 351 (7), 898-900
PubMed 5432756
[Drug effects on enzyme synthesis]
Tidsskr Nor Laegeforen, 90 (2), 208-10
PubMed 4914233
Publications 1969
Tyrosine transaminase degradation in perfused liver after inhibition of protein synthesis by cycloheximide
Biochim Biophys Acta, 174 (1), 398-400
DOI 10.1016/0005-2787(69)90266-4, PubMed 4387935
Tryptophan oxygenase activation and ascorbate oxidation in whole homogenates from rat liver
Biochim Biophys Acta, 171 (1), 47-57
DOI 10.1016/0005-2744(69)90104-1, PubMed 5763409
A simple perfusion technique applied to glucocorticoid regulation of tryptophan oxygenase turnover and bile production in the isolated rat liver
Hoppe Seylers Z Physiol Chem, 350 (3), 308-16
DOI 10.1515/bchm2.1969.350.1.308, PubMed 5769958
Publications 1968
Insulin inhibition of tyrosine transaminase degradation in the isolated, perfused rat liver
Hoppe Seylers Z Physiol Chem, 349 (9), 1229-30
PubMed 4387600
[The history of instruments for cleaning the teeth]
Nor Tannlaegeforen Tid, 78 (5), 301-8
PubMed 4876473
Tannrensingsinstrumentenes historie
Fabritius, Oslo, S. 301-308
BIBSYS 021438315