WIF-B cells as a model for alcohol-induced hepatocyte injury
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- 作者：Schaffert ; Courtney S. ; Todero ; Sandra L. ; McVicker ; Benita L. ; Tuma ; Pamela L. ; Sorrell ; Michael F. ; et. al.
- 关键词：ADH ; alcohol dehydrogenase ; ALDH ; aldehyde dehydrogenase ; CYP2E1 ; cytochrome P4502E1 ; 4-MP ; 4-methylpyrazole ; WIF-B cells ; Alcohol dehydrogenase ; Triglycerides ; Ethanol metabolism ; Liver injury ; Cytochrome P4502E1
- 刊名：Biochemical Pharmacology
- 出版年：2004
- 出版时间：June 1, 2004
- 年：2004
- 卷：67
- 期：11
- 页码：2167-2174
- 全文大小：341 K
文摘
A potential in vitro model for studying the mechanisms of alcohol-induced hepatocyte injury is the WIF-B cell line. It has many hepatocyte-like features, including a differentiated, polarized phenotype resulting in formation of bile canaliculi. The aim of this study was to examine the effects of ethanol treatment on this cell line. WIF-B cells were cultured up to 96h in the absence or presence of 25mM ethanol and subsequently were analyzed for ethanol-induced physiological and morphological changes. Initial studies revealed WIF-B cells exhibited alcohol dehydrogenase (ADH) activity, expressed cytochrome P4502E1 (CYP2E1), and efficiently metabolized ethanol in culture. This cell line also produced the ethanol metabolite acetaldehyde and exhibited low Km aldehyde dehydrogenase (ALDH) activity, comparable to hepatocytes. Ethanol treatment of the WIF-B cells for 48h led to significant increases in the lactate/pyruvate redox ratio and cellular triglyceride levels. Ethanol treatment also significantly altered WIF-B morphology, decreasing the number of bile canaliculi, increasing the number of cells exhibiting finger-like projections, and increasing cell diameter. The ethanol-induced changes occurring in this cell line were negated by addition of the ADH inhibitor, 4-methylpyrazole (4-MP), indicating the effects were due to ethanol metabolism. In summary, the WIF-B cell line metabolizes ethanol and exhibits many ethanol-induced changes similar to those found in hepatocytes. Because of these similarities, WIF-B cells appear to be a suitable model for studying ethanol-induced hepatocyte injury.