HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics

2014 ◽  
Vol 38 (5) ◽  
pp. 691-704 ◽  
Author(s):  
Jong Min Choi ◽  
Soo Jin Oh ◽  
Sang Yoon Lee ◽  
Ji Hye Im ◽  
Jung Min Oh ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Hepg2 Cells ◽  
In Vitro Model ◽  
Cytochrome P450 Induction ◽  
Vitro Model

Utility of Long-Term Cultured Human Hepatocytes as an in Vitro Model for Cytochrome P450 Induction

2006 ◽  
Vol 35 (2) ◽  
pp. 215-220 ◽  
Author(s):  
Georgina Meneses-Lorente ◽  
Christine Pattison ◽  
Claire Guyomard ◽  
Christophe Chesné ◽  
Robert Heavens ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

CRYOPRESERVED HUMAN HEPATOCYTES AS ALTERNATIVE IN VITRO MODEL FOR CYTOCHROME P450 INDUCTION STUDIES

2003 ◽  
Vol 39 (7) ◽  
pp. 283 ◽  
Author(s):  
MARTHA GARCIA ◽  
JOSEPH RAGER ◽  
QING WANG ◽  
ROBERT STRAB ◽  
ISMAEL J. HIDALGO ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

CRYOPRESERVED HUMAN HEPATOCYTES AS ALTERNATIVE IN VITRO MODEL FOR CYTOCHROME P450 INDUCTION STUDIES

2003 ◽  
Author(s):  
Martha Garcia ◽  
Joseph Rager ◽  
Qing Wang ◽  
Robert Strab ◽  
Ismael Hidalgo ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Vitro Model ◽  
Human Hepatocytes ◽  
Cytochrome P450 Induction ◽  
Vitro Model

Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells

2014 ◽  
Vol 445 (1) ◽  
pp. 236-243 ◽  
Author(s):  
Tomoyuki Yuasa ◽  
Kikuko Amo ◽  
Shuhei Ishikura ◽  
Hisao Nagaya ◽  
Keiji Uchiyama ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
High Glucose ◽  
Hepg2 Cells ◽  
In Vitro Model ◽  
Vitro Model

scholarly journals SUN-550 CARF Through Its Lipid Lowering Effect May Play a Pivotal Role in the Development of Non-Alcoholic Fatty Liver Diseases

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Amiya P Sinha-Hikim ◽  
Theodore C Friedman
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Hepg2 Cells ◽  
In Vitro Model ◽  
Lipid Lowering ◽  
Alcoholic Fatty Liver ◽  
Lowering Effect ◽  
Vitro Model ◽  
Lipid Lowering Effect

Abstract CARF (Collaborator of ARF), a member of ARF-MDM2-p53 pathway and an emerging multifunctional protein, regulates cellular fate in response to various stresses including oxidative DNA damage and replicative stresses. However, its role in metabolic syndrome (MS) and associated diseases has not been studied. This study, using our well established in vivo and in vitro model systems, examines the role of CARF in the development of non-alcoholic fatty liver disease (NAFLD). Indeed, we have found that, compared to control, CARF expression along with Sirt1, pAMPK and pACC (common biological markers of NAFLD) was significantly decreased in the nicotine and high-fat-diet (HFD) in combination or HFD alone induced fatty livers. Additionally, CARF expression was down regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis, suggesting that CARF expression is negatively regulated in MS, such as NAFLD. Our study further revealed that shRNA mediated knockdown or lentiviral mediated over expression of CARF induced or reduced endogenous fat accumulation, respectively, in HepG2 cells. We also found that overexpression of CARF lowered the exogenous fat accumulation in PA treated HepG2 cells. RNA seq analysis after CARF knockdown in HEK-293T cells further revealed that genes associated with lipid metabolism and triglyceride (TG) synthesis such as diacylglycerol O-acyltransferase2 (DGAT2), acyl-CoA synthetase long-chain family member 4 and 6 (ACSL4, ACSL6) were upregulated in CARF-depleted cells. Likewise, we also found increased expression of DGAT2 in CARF-depleted HepG2 cells, which enhanced TG synthesis. Intriguingly, consistent with the lipid lowering effects of metformin, an antidiabetic drug, we further found that CARF expression along with pAMPK and Sirt1 were significantly increased in metformin-treated HepG2 cells. However, we also found increased pACC levels in CARF over-expressing cells which was further enhanced in metformin-treated cells, suggesting, for the first time, that CARF may contribute to lipid lowering effect of metformin by inhibiting lipogenesis. We conclude that CARF has a lipid lowering effect in hepatocytes and its down regulation in response to MS perturbs lipid metabolism that may lead to the development of NAFLD.

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