کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911631 1046825 2017 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative stress induces actin-cytoskeletal and tight-junctional alterations in hepatocytes by a Ca2+-dependent, PKC-mediated mechanism: Protective effect of PKA
ترجمه فارسی عنوان
استرس اکسیداتیو باعث اکتین اسکلت سلولی و تغییرات سیناپسی تنگ در سلول‌های کبدی توسط Ca2 + وابسته، مکانیسم واسطه به PKC می شود: اثر حفاظتی PKA
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی

Oxidative stress elevates Ca2+ and, presumably, activates Ca2+-dependent PKCs. We analyzed the participation of Ca2+-dependent PKCs in actin disorganization and tight-junctional impairment induced by the pro-oxidant tert-butylhydroperoxide (tBOOH) in isolated rat hepatocyte couplets. tBOOH (100 μM) augmented radical oxygen species (ROS), as indicated by increased lipid peroxidation (+217%, p < 0.05) and intracellular production of 2′,7′-dichlorofluorescein (+36%, p < 0.05). Cytosolic Ca2+ and PKCα translocation to membrane, an indicator of PKCα activation, were also elevated by tBOOH (+100 and +79%, respectively, p < 0.05). tBOOH increased the number of couplets displaying membrane blebs (+278%, p < 0.001) and caused redistribution of F-actin. tBOOH induced tight-junctional impairment, as indicated by a reduction in the percentage of couplets retaining presecreted cholyllysylfluorescein in their canalicular vacuoles (−54%, p < 0.001). tBOOH induced redistribution of the tight-junctional-associated protein ZO-1. All these events were prevented by the panspecific PKC inhibitors H7 and staurosporine, the Ca2+-dependent PKC inhibitor Gö6976, the intracellular Ca2+ chelator BAPTA/AM, and the PKA activator dibutyryl-cyclic AMP. Furthermore, PKC inhibition and PKA activation not only prevented but also fully reversed tBOOH-induced blebbing. Conversely, tBOOH-induced ROS formation and Ca2+ elevation remained unchanged. We conclude that ROS induce hepatocellular actin-cytoskeleton rearrangement and tight-junctional impairment by a PKC-mediated, Ca2+-dependent mechanism, which is counteracted by PKA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 40, Issue 11, 1 June 2006, Pages 2005–2017
نویسندگان
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