کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859038 1562323 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Redistribution of subcellular calcium and its effect on apoptosis in primary cultures of rat proximal tubular cells exposed to lead
ترجمه فارسی عنوان
توزیع کلسیم زیر سلولی و تأثیر آن در آپوپتوز در کشت اولیه سلول های لوله ای پروگزیمال موش صحرایی در معرض سرب
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Previous studies have shown that cytosolic Ca2+ ([Ca2+]c) overload was involved in Pb-induced apoptosis in primary cultures of rat proximal tubular (rPT) cells, but the source of elevated Ca2+ and the effect of potential subcellular Ca2+ redistribution on apoptosis are still unknown. In this study, variations of [Ca2+]c in two culture media (Ca2+-containing and Ca2+- free) were analyzed, indicating that Pb-induced elevation of [Ca2+]c was primarily generated intracellularly. Fluo-4-AM, dihydro-Rhod-2-AM and Mag-Fluo-4-AM was loaded to Pb-exposed rPT cells to monitor the imaging of Ca2+ concentrations in the cytoplasm ([Ca2+]c), mitochondria ([Ca2+]mit) and endoplasmic reticulum (ER) ([Ca2+]ER), respectively, under the confocal microscope. Data indicate that elevations of [Ca2+]c and [Ca2+]mit with depletion of [Ca2+]ER were revealed in Pb-treated rPT cells, but this subcellular Ca2+ redistribution could be significantly suppressed by 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor (IP3R) that functions to release Ca2+ from ER stores. Simultaneously, Pb-mediated mitochondrial Ca2+ overload can be partially suppressed by the cytosolic Ca2+ chelator BAPTA-AM, suggesting that Ca2+ uptake into mitochondria occurs via diverse pathways and ER Ca2+ storage was the chief source. Furthermore, Pb-induced apoptosis was markedly inhibited by 2-APB and BAPTA-AM, respectively. Additionally, elevated IP3 levels with up-regulated IP3R-1 and IP3R-2 (mRNA and protein) levels were revealed in Pb-exposed rPT cells. In summary, IP3R-mediated ER Ca2+ release promoted the elevations of [Ca2+]c and [Ca2+]mit in Pb-exposed rPT cells, which played a chief role in apoptosis induced by impaired calcium homeostasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 333, 3 July 2015, Pages 137-146
نویسندگان
, , , , , , ,