کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2532831 1559030 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
2′,4′,6′-Tris(methoxymethoxy) chalcone induces apoptosis by enhancing Fas-ligand in activated hepatic stellate cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
2′,4′,6′-Tris(methoxymethoxy) chalcone induces apoptosis by enhancing Fas-ligand in activated hepatic stellate cells
چکیده انگلیسی

Suppression of hepatic stellate cell (HSC) activation and proliferation, and induction of apoptosis in activated HSCs have been proposed as therapeutic strategies for the treatment and prevention of the hepatic fibrosis. We previously showed that 2′,4′,6′-tris(methoxymethoxy) chalcone (TMMC), a synthesized chalcone derivative, inhibits platelet-derived growth factor-induced HSC proliferation at 5–20 μM. Here, we showed that TMMC induces apoptosis in activated HSCs at higher concentrations (30–50 μM), but is not cytotoxic to primary hepatocytes. Moreover, TMMC induces hyperacetylation of histone by inhibiting histone deacetylase (HDAC) in activated HSCs. Interestingly, TMMC treatment remarkably increased Fas-ligand (FasL) mRNA expression in a dose-dependent manner. Cycloheximide treatment reversed the induction of TMMC on apoptosis, indicating that de novo protein synthesis was required for TMMC-induced apoptosis in activated HSCs. In addition, FasL synthesis by TMMC is closely associated with maximal procaspase-3 proteolytic processing. In vivo, TMMC reduced activated HSCs in CCl4-intoxicated rats during liver injury recovery, as demonstrated by α-smooth muscle actin expression in rat liver. TMMC treatment also resulted in apoptosis, as demonstrated by cleavage of poly(ADP-ribose) polymerase in rat liver. In conclusion, TMMC may have therapeutic potential by inducing HSC apoptosis for the treatment of hepatic fibrosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 658, Issue 1, 1 May 2011, Pages 9–15
نویسندگان
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