کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9002487 | 1118588 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of protein kinase Cδ by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2
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کلمات کلیدی
DMEMZ-DEVD-FMKPC12MnCl2PKCDulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoROS - ROSz-VAD-fmk - Z-VAD-FMKEnzyme-Linked Immuno-Sorbent Assay - آنزیم مرتبط با ایمونوسیبنیتهGene delivery - انتقال ژن benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone - بنزیلوکسیکربنیل-وال-آلا-آسپ-فلورومتیلیکونParkinson's disease - بیماری پارکینسونELISA - تست الیزاOxidative stress - تنش اکسیداتیوRat pheochromocytoma cells - سلولهای فئوکروموسیتوما موش صحراییManganese - منگنز Mitochondria - میتوکندریاProtein kinase C - پروتئین کیناز سیmanganese chloride - کلرید منگنزReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Activation of protein kinase Cδ by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2 Activation of protein kinase Cδ by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2](/preview/png/9002487.png)
چکیده انگلیسی
Chronic inorganic manganese exposure causes selective toxicity to the nigrostriatal dopaminergic system, resulting in a Parkinsonian-like neurological condition known as Manganism. Apoptosis has been shown to occur in manganese-induced neurotoxicity; however, the down-stream cellular target of caspase-3 that contributes to DNA fragmentation is not established. Herein, we demonstrate that proteolytic activation of protein kinase Cδ (PKCδ) by caspase-3 plays a critical role in manganese-induced apoptotic cell death. Treatment of PC12 cells with manganese caused a sequential activation of mitochondrial-dependent pro-apoptotic events, including mitochondrial membrane depolarization, cytochrome c release, caspase-3 activation, and DNA fragmentation. Overexpression of Bcl-2 in PC12 cells remarkably attenuated each of these events, indicating that the mitochondrial-dependent apoptotic cascade contributes to manganese-induced apoptosis. Furthermore, PKCδ was proteolytically cleaved by caspase-3, causing a persistent activation of the kinase. The manganese-induced proteolytic cleavage of PKCδ was significantly blocked by Bcl-2-overexpression. Administration of active recombinant PKCδ induced DNA fragmentation in PC12 cells, suggesting a pro-apoptotic role of PKCδ. Furthermore, expression of catalytically inactive mutant PKCδK376R via a lentiviral gene delivery system effectively attenuated manganese-induced apoptosis. Together, these results suggest that the mitochondrial-dependent caspase cascade mediates apoptosis via proteolytic activation of PKCδ in manganese-induced neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 1, 1 January 2005, Pages 133-146
Journal: Biochemical Pharmacology - Volume 69, Issue 1, 1 January 2005, Pages 133-146
نویسندگان
Masashi Kitazawa, Vellareddy Anantharam, Yongjie Yang, Yoko Hirata, Arthi Kanthasamy, Anumantha G. Kanthasamy,