Mechanistic evaluation of primary human hepatocyte culture using global proteomic analysis reveals a selective dedifferentiation profile

Archives of Toxicology

Volumn 91, Issue 1, 2017, Pages 439-452

  Heslop, James A ^a   Rowe, Cliff ^b   Walsh, Joanne ^a   Sison Young, Rowena ^a   Jenkins, Roz ^a   Kamalian, Laleh ^a   Kia, Richard ^a   Hay, David ^a   Jones, Robert P ^c   Malik, Hassan Z ^c   Fenwick, Stephen ^c   Chadwick, Amy E ^a   Mills, John ^d   Kitteringham, Neil R ^a   Goldring, Chris E P ^a   Kevin Park, B ^a  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY HOSPITAL AINTREE   (United Kingdom)

^d ASTRAZENECA   (United Kingdom)

Author keywords

Cytochrome P450s; Donor variation; Human hepatocytes; iTRAQ; Mass spectrometry; Mitochondria

Indexed keywords

CYTOCHROME P450; MITOCHONDRIAL PROTEIN; PROTEOME; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); ROTENONE; UNCOUPLING PROTEIN;

ARTICLE; CELL DEDIFFERENTIATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IN VITRO STUDY; INTRACELLULAR SIGNALING; LIVER CELL; LIVER CELL CULTURE; MONOLAYER CULTURE; PRIMARY CELL CULTURE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEOMICS; QUANTITATIVE ANALYSIS; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CYTOLOGY; DRUG EFFECTS; ENZYMOLOGY; EVALUATION STUDY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; KINETICS; LIVER MITOCHONDRION; METABOLISM; PHARMACOLOGY; PROCEDURES; PROTEIN STABILITY; REPRODUCIBILITY; TOXICOLOGY;

CELL DEDIFFERENTIATION; CELLS, CULTURED; ELECTRON TRANSPORT COMPLEX I; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HEPATOCYTES; HUMANS; KINETICS; MITOCHONDRIA, LIVER; PHARMACOLOGY; PROTEIN STABILITY; PROTEOME; REPRODUCIBILITY OF RESULTS; ROTENONE; TOXICOLOGY; UNCOUPLING AGENTS;

EID: 84962016926     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-016-1694-y     Document Type: Article

References (44)

1. Allen JW, Khetani SR, Bhatia SN (2005) In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol Sci 84(1):110–119. doi:10.1093/toxsci/kfi052
2. Bhogal RH, Hodson J, Bartlett DC et al (2011) Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience. PLoS ONE 6(3):e18222. doi:10.1371/journal.pone.0018222
3. Darnell M, Ulvestad M, Ellis E, Weidolf L, Andersson TB (2012) In vitro evaluation of major in vivo drug metabolic pathways using primary human hepatocytes and HepaRG cells in suspension and a dynamic three-dimensional bioreactor system. J Pharmacol Exp Ther 343(1):134–144
4. Elaut G, Henkens T, Papeleu P et al (2006) Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr Drug Metab 7(6):629–660
5. Fraczek JE, Vinken M, Tourwe D, Vanhaecke T, Rogiers V (2012) Synergetic effects of DNA demethylation and histone deacetylase inhibition in primary rat hepatocytes. Invest New Drugs 30(4):1715–1724. doi:10.1007/s10637-011-9659-8
6. Fraczek J, Bolleyn J, Vanhaecke T, Rogiers V, Vinken M (2013) Primary hepatocyte cultures for pharmaco-toxicological studies: at the busy crossroad of various anti-dedifferentiation strategies. Arch Toxicol 87(4):577–610. doi:10.1007/s00204-012-0983-3
7. Fu D, Mitra K, Sengupta P, Jarnik M, Lippincott-Schwartz J, Arias IM (2013) Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization. Proc Natl Acad Sci 110(18):7288–7293. doi:10.1073/pnas.1304285110
8. Godoy P, Hengstler JG, Ilkavets I et al (2009) Extracellular matrix modulates sensitivity of hepatocytes to fibroblastoid dedifferentiation and transforming growth factor beta-induced apoptosis. Hepatology 49(6):2031–2043
9. Godoy P, Hewitt NJ, Albrecht U et al (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87(8):1315–1530
10. Gresh L, Bourachot B, Reimann A et al (2005) The SWI/SNF chromatin-remodeling complex subunit SNF5 is essential for hepatocyte differentiation. EMBO J 24(18):3313–3324. doi:10.1038/sj.emboj.7600802
11. Guo L, Dial S, Shi L et al (2011) Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes. Drug Metab Dispos 39(3):528–538. doi:10.1124/dmd.110.035873
12. Jiang Q, Yan Z, Feng J (2006) Neurotrophic factors stabilize microtubules and protect against rotenone toxicity on dopaminergic neurons. J Biol Chem 281(39):29391–29400. doi:10.1074/jbc.M602740200
13. Jungermann K, Kietzmann T (1996) Zonation of parenchymal and nonparenchymal metabolism in liver. Annu Rev Nutr 16:179–203. doi:10.1146/annurev.nu.16.070196.001143
14. Kia R, Sison RL, Heslop J et al (2013) Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet? Br J Clin Pharmacol 75(4):885–896
15. Kim Y, Lasher CD, Milford LM, Murali TM, Rajagopalan P (2010) A comparative study of genome-wide transcriptional profiles of primary hepatocytes in collagen sandwich and monolayer cultures. Tissue Eng Part C Methods 16(6):1449–1460
16. Lasher CD, Rajagopalan P, Murali TM (2011) Discovering networks of perturbed biological processes in hepatocyte cultures. PLoS ONE 6(1):0015247
17. LeCluyse EL, Alexandre E, Hamilton GA et al (2005) Isolation and culture of primary human hepatocytes. Methods Mol Biol 290:207–229
18. Leppä S, Pirkkala L, Saarento H, Sarge KD, Sistonen L (1997) Overexpression of HSF2-β inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells. J Biol Chem 272(24):15293–15298. doi:10.1074/jbc.272.24.15293
19. Marinescu VD, Kohane IS, Riva A (2005) The MAPPER database: a multi-genome catalog of putative transcription factor binding sites. Nucleic Acids Res 33(Suppl 1):D91–D97. doi:10.1093/nar/gki103
20. Mi H, Muruganujan A, Casagrande JT, Thomas PD (2013) Large-scale gene function analysis with the PANTHER classification system. Nat Protoc 8(8):1551–1566
21. Mobus S, Yang D, Yuan Q et al (2015) MicroRNA-199a-5p inhibition enhances the liver repopulation ability of human embryonic stem cell-derived hepatic cells. J Hepatol 62(1):101–110. doi:10.1016/j.jhep.2014.08.016
22. Muppala V, Lin C-S, Lee Y-H (2000) The role of HNF-1α in controlling hepatic catalase activity. Mol Pharmacol 57(1):93–100
23. Naiki T, Nagaki M, Asano T, Kimata T, Moriwaki H (2005) Adenovirus-mediated hepatocyte nuclear factor-4alpha overexpression maintains liver phenotype in cultured rat hepatocytes. Biochem Biophys Res Commun 335(2):496–500. doi:10.1016/j.bbrc.2005.07.102
24. No DY, Lee S-A, Choi YY et al (2012) Functional 3D human primary hepatocyte spheroids made by co-culturing hepatocytes from partial hepatectomy specimens and human adipose-derived stem cells. PLoS ONE 7(12):e50723. doi:10.1371/journal.pone.0050723
25. Odom DT, Zizlsperger N, Gordon DB et al (2004) Control of pancreas and liver gene expression by HNF transcription factors. Science 303(5662):1378–1381. doi:10.1126/science.1089769
26. Padgham CR, Boyle CC, Wang XJ, Raleigh SM, Wright MC, Paine AJ (1993) Alteration of transcription factor mRNAs during the isolation and culture of rat hepatocytes suggests the activation of a proliferative mode underlies their de-differentiation. Biochem Biophys Res Commun 197(2):599–605. doi:10.1006/bbrc.1993.2521
27. Papp B, Plath K (2013) Epigenetics of reprogramming to induced pluripotency. Cell 152(6):1324–1343. doi:10.1016/j.cell.2013.02.043
28. Rambhatla L, Chiu CP, Kundu P, Peng Y, Carpenter MK (2003) Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transpl 12(1):1–11
29. Richert L, Liguori MJ, Abadie C et al (2006) Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating. Drug Metab Dispos 34(5):870–879. doi:10.1124/dmd.105.007708
30. Ripple MO, Kim N, Springett R (2013) Acute mitochondrial inhibition by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitors regulates proliferation. J Biol Chem 288(5):2933–2940. doi:10.1074/jbc.M112.430082
31. Ritchie ME, Phipson B, Wu D et al (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47. doi:10.1093/nar/gkv007
32. Rodriguez-Antona C, Donato MT, Boobis A et al (2002) Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells. Xenobiotica 32(6):505–520. doi:10.1080/00498250210128675
33. Rowe C, Goldring CE, Kitteringham NR et al (2010) Network analysis of primary hepatocyte dedifferentiation using a shotgun proteomics approach. J Proteome Res 9(5):2658–2668
34. Rowe C, Gerrard DT, Jenkins R et al (2013) Proteome-wide analyses of human hepatocytes during differentiation and dedifferentiation. Hepatology 58(2):799–809. doi:10.1002/hep.26414
35. Schwanhausser B, Busse D, Li N et al (2011) Global quantification of mammalian gene expression control. Nature 473(7347):337–342
36. Shan J, Schwartz RE, Ross NT et al (2013) Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 9(8):514–520
37. Singh G, Veltri KL (1991) A mechanism for the loss of cytochrome P-450 in primary mouse hepatocytes. Mol Cell Biochem 108(2):151–156
38. Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H, Sajantila A (2009) Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics 19(2):170–179. doi:10.1097/FPC.0b013e32831ebb30
39. Thomas S, Bonchev D (2010) A survey of current software for network analysis in molecular biology. Hum Genomics 4(5):353–360
40. Tostoes RM, Leite SB, Serra M et al (2012) Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing. Hepatology 55(4):1227–1236
41. Wilson BG, Roberts CWM (2011) SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 11(7):481–492
42. Yousefi B, Darabi M, Baradaran B et al (2012) Inhibition of MEK/ERK1/2 signaling affects the fatty acid composition of HepG2 human hepatic cell line. BioImpacts: BI 2(3):145–150. doi:10.5681/bi.2012.019
43. Zamek-Gliszczynski MJ, Hoffmaster KA, Tweedie DJ, Giacomini KM, Hillgren KM (2012) Highlights from the international transporter consortium second workshop. Clin Pharmacol Ther 92(5):553–556. doi:10.1038/clpt.2012.126
44. Zellmer S, Schmidt-Heck W, Godoy P et al (2010) Transcription factors ETF, E2F, and SP-1 are involved in cytokine-independent proliferation of murine hepatocytes. Hepatology 52(6):2127–2136