التفاصيل البيبلوغرافية
| العنوان: |
The Resveratrol Attenuates Ethanol-Induced Hepatocyte Apoptosis Via Inhibiting ER-Related Caspase-12 Activation and PDE Activity In Vitro. |
| المؤلفون: |
Liu, LQ, Fan, ZQ, Tang, YF, Ke, ZJ |
| المصدر: |
Alcoholism: Clinical & Experimental Research; Mar2014, Vol. 38 Issue 3, p683-693, 11p |
| مصطلحات موضوعية: |
ANALYSIS of variance, APOPTOSIS, BIOLOGICAL assay, CELL culture, CELL physiology, CELLULAR signal transduction, ESTERASES, ETHANOL, FLUORESCENT antibody technique, GENES, GENETIC polymorphisms, LIVER, OXIDOREDUCTASES, POLYMERASE chain reaction, PROTEOLYTIC enzymes, RESEARCH funding, T-test (Statistics), WESTERN immunoblotting, RESVERATROL, DATA analysis software, DESCRIPTIVE statistics, IN vitro studies |
| مستخلص: |
Background Endoplasmic reticulum ( ER) stress plays a key role in cell apoptosis pathways. Caspase-12, a proapoptotic gene induced by ER stress, is also the key molecule in ER-related apoptosis. The purpose of this study is to evaluate the protective activity and possible mechanism of resveratrol (ResV) against ethanol ( Et OH)-induced apoptosis in human hepatocyte Chang cell line. Methods The human hepatocyte Chang cell line was used to test the hypothesis that Res V may alleviate the liver cell apoptosis induced by Et OH. ER stress-inducible proteins and silent mating type information regulation 2 homolog 1 (SIRT1) were assayed by Western blot. Cell viability was studied by MTT assay and apoptosis was measured by Annexin- V and propidium iodide assay. Caspase-12 activation was examined by immunofluorescence staining. Alcohol dehydrogenase-2 ( ADH-2) and aldehyde dehydrogenase-2 ( ALDH-2) were measured by polymerase chain reaction amplified product length polymorphism. Phosphodiesterase (PDE) activity was assayed in cell lysates using a cyclic nucleotide PDE assay. Results EtOH exposure significantly increased the expression of ER stress markers and activated signaling pathways associated with ER stress. These include GRP78, p-IRE1α, p- eIF2α, p-PERK, ATF4 as well as cleaved caspase-3/12, CHOP/GADD153, and Bax in human hepatocyte Chang cell line. The expression of these proteins were significantly down-regulated by ResV (10 μM) in a SIRT1-dependent manner. ResV can inhibit EtOH-, tunicamycin-, thapsigargin-induced caspase-12 activation. ADH-2 and ALDH-2 activities are lower in this cell line. PDE activity increased by EtOH was inhibited by ResV (10 μM). Conclusions The results indicate that (i) EtOH-induced activation of caspase-12 could be one of the underlying mechanisms of hepatocyte apoptosis; (ii) EtOH-induced cell apoptosis was alleviated via ResV (10 μM) by inhibiting ER stress and caspase-12 activation in a SIRT1-dependent manner; and (iii) SIRT1 activated indirectly by ResV (10 μM) attenuates EtOH-induced hepatocyte apoptosis partly through inhibiting PDE activity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
