کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8538990 | 1561124 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pb2Â + modulates ryanodine receptors from the endoplasmic reticulum in rat brain
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کلمات کلیدی
GSHpKaBmaxcADPRRyRsMg2 +Radioligand binding assayscyclic ADP-ribose - ADP-ribose cyclicCa2 + - Ca2 +Sarcoplasmic reticulum - رتیکولوم سارکوپلاسمیکendoplasmic reticulum - شبکه آندوپلاسمی cAMP-dependent protein kinase A - پروتئین کیناز A وابسته به cAMPreduced glutathione - کاهش گلوتاتیونRyanodine receptors - گیرنده های رایانودین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Although the neurotoxic mechanism of lead (Pb2 +) has been extensively studied, it is not well understood. The effects of Pb2 + on free cytosolic calcium (Ca2 +) concentration and calcium-regulated events have been suggested to be major mechanisms in Pb2 + toxicity. Based on our previous findings that Pb2 + changes calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic reticulum (ER) vesicular RyRs by Pb2 + was investigated further in the present study. The results of [3H]ryanodine binding assays showed that in the presence of a free Ca2 + concentration ([Ca2 +]f) of 100 μM, Pb2 + modulated the equilibrium of [3H]ryanodine binding to brain RyRs, with a U-type dose-response curve, where minimal binding was observed at a free Pb2 + concentration ([Pb2 +]f) of 0.39 μM. This modulation was also observed over a time course. Scatchard analysis indicated that both an increase in Kd and a possible decrease in Bmax were responsible for the decrease in binding induced by low [Pb2 +]f. Moreover, the effects of Pb2 + on the function of ER RyRs in neurons might also be controlled by other RyR modulators. Whole-cell patch-clamp experiments revealed that dynamic calcium oscillations evoked by specific RyR agonists were depressed rapidly and reversibly by exposure to 10 μM Pb2 +. Our study indicates that RyRs are molecular targets of Pb2 +, and this interaction disturbs Ca2 + signals and leads to neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 103-111
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 103-111
نویسندگان
Qiyue Jia, Guihua Du, Yu Li, Zhiping Wang, Jie Xie, Junwang Gu, Guangming Yin, Shuyun Zhang, Yanyan Gao, Fankun Zhou, Chang Feng, Guangqin Fan,