کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10958050 | 1099961 | 2013 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes
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کلمات کلیدی
LPSCA-4JnkCHXPKCERKpKaGJIC2(5H)-Furanone - 2 (5H) -Furanonec-Jun N-terminal protein kinase - C-Jun N-terminal protein kinaseJAK/STAT - JAK / STATMAPK - MAPKAstrocyte - آستروسیتGap junction intercellular communication - ارتباط بین سلولی Gap junctionMicrotubule - ریزلوله یا میکروتوبولcycloheximide - سیکلوهایسیمیدSignaling - سیگنالینگgap junction - فاصله ی شکافlipopolysaccharide - لیپوپلی ساکاریدprotein kinase A - پروتئین کیناز AProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogencombretastatin A-4 - کمبرتستاتین A-4extracellular-regulated kinase - کیناز تنظیم شده خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression. A confocal microscopic study and scrape-loading/dye transfer analyses demonstrated that HYS-32 (5 μM) induced microtubule coiling, accumulation of Cx43 in gap junction plaques, and increased GJIC in astrocytes. The HYS-32-induced microtubule coiling and Cx43 accumulation in gap junction plaques was reversed when HYS-32 was removed. Treatment of astrocytes with cycloheximide resulted in time-dependent degradation of by co-treatment with HYS-32 by increasing the half-life of Cx43. Co-treatment with HYS-32 also prevented the LPS-induced downregulation of Cx43 and inhibition of GJIC in astrocytes. HYS-32 induced activation of PKC, ERK, and JNK, and co-treatment with the PKC inhibitor Go6976 or the ERK inhibitor PD98059, but not the JNK inhibitor SP600125, prevented the HYS-32-induced increase in Cx43 expression and GJIC. Go6976 suppressed the HYS-32-induced PKC phosphorylation and increase in phospho-ERK levels, while PD98059 did not prevent the HYS-32-induced increase in phospho-PKC levels, suggesting that PKC is an upstream effector of ERK. In conclusion, our results show that HYS-32 increases the half-life of Cx43 and enhances Cx43 expression and GJIC in astrocytes via a PKC-ERK signaling cascade. These novel biological effects of HYS-32 on astrocyte gap junctions support its potential for therapeutic use as a protective agent for the central nervous system.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 62, Issue 6, May 2013, Pages 881-892
Journal: Neurochemistry International - Volume 62, Issue 6, May 2013, Pages 881-892
نویسندگان
Pei-Chun Lin, Chien-Chang Shen, Chih-Kai Liao, Guey-Mei Jow, Chi-Ting Chiu, Tun-Hui Chung, Jiahn-Chun Wu,