ALTERATION OF CYP3A1 mRNA LEVEL IN PRIMARY RAT HEPATOCYTES IN RESPONSE TO AMPK ACTIVE ATOR AICAR

Main Article Content

Bang-Sub Lee
Jooyoung Kim
Wi-Young So

Keywords

5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside, AMP-activated protein kinase, CYP3A1

Abstract

Background and Objective


AMP-activated protein kinase (AMPK) functions as a sensor of the intracellular energy status that can be stimulated by a synthetic activator, 5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside (AICAR), which is used to replicate the effect of physical exercise in hepatocyte embryoid bodies. This study investigated the effect of AICAR on the CYP3A1 mRNA expression in primary hepatocyte embryoid bodies derived from a rat liver.


Material and Methods


The primary hepatocytes were isolated from a male Sprague Dawley (SD) rat (215 g) and subjected to the following treatments: control without AICAR (CTL, n=3), 1 μM AICAR (n=3), 10 μM AICAR (n=3), and 100 μM AICAR (n=3). RNA was isolated and used as the template for synthesizing cDNA by reverse transcriptase to perform quantitative PCR (qPCR). The independent samples t-test was conducted to examine differences between groups. Statistical significance was set at p<0.05.


Results


The qPCR analysis demonstrated that CYP3A1 mRNA expression in primary hepatocyte embryoid bodies significantly increased in the presence of 10 μM (t=1.730, p<0.05) and 100 μM AICAR (t=3.207, p<0.05) as compared to that in the control group hepatocytes. However, the observed increase of CYP3A1 mRNA in hepatocyte embryoid bodies was not statistically significant in the presence of 1 μM AICAR as the lowest test concentration.


Conclusion


In this study, we demonstrated that AICAR, an AMPK activator, can increase the expression of CYP3A1 mRNA in primary hepatocytes. Future studies should assess the effect of AICAR treatment on CYP3A4 in human hepatocytes.

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