کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1910173 | 1046756 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5
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کلمات کلیدی
5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetateDAPIN-acetyl-l-cysteinePP2ANACPARPASK1PDLPP5CM-H2DCFDAMKP1zVAD-fmkFBSJnkDMEMPBS4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولc-Jun N-terminal kinase - C-Jun N-terminal kinaseDulbecco's modified Eagle Medium - Eagle Medium اصلاح شده DulbeccoERK1/2 - ERK1 / 2MAPK - MAPKMAPK kinase - MAPK کینازMKK - MCCROS - ROSHydrogen peroxide - آب اکسیژنهamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکAlzheimer's disease - بیماری آلزایمرALS - بیماری اسکلروز جانبی آمیوتروفیکParkinson's disease - بیماری پارکینسونApoptosis - خزان یاختهایfetal bovine serum - سرم جنین گاوPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریH2O2 - هیدروژن پراکسیدprotein phosphatase 2A - پروتئین فسفاتاز 2Aprotein phosphatase 5 - پروتئین فسفاتاز 5mitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPropidium iodide - پروتئین یدیدpoly (ADP-ribose) polymerase - پلی (ADP-ribose) پلیمرازPoly-d-lysine - پلی دی لیزینoptical density - چگالی نوریCadmium - کادمیمextracellular signal-regulated kinase 1/2 - کیناز 1/2 تنظیم سیگنال خارج سلولیapoptosis signal-regulating kinase 1 - کیناز تنظیم کننده سیگنال آپوپتوز 1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cadmium (Cd), a highly toxic environmental pollutant, induces neurodegenerative diseases. Recently we have demonstrated that Cd may induce neuronal apoptosis in part through activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (Erk1/2) pathways. However, the underlying mechanism remains enigmatic. Here we show that Cd induced generation of reactive oxygen species (ROS), leading to apoptosis of PC12 and SH-SY5Y cells. Pretreatment with N-acetyl-L-cysteine (NAC) scavenged Cd-induced ROS, and prevented cell death, suggesting that Cd-induced apoptosis is attributed to its induction of ROS. Furthermore, we found that Cd-induced ROS inhibited serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5), leading to activation of Erk1/2 and JNK, which was abrogated by NAC. Overexpression of PP2A or PP5 partially prevented Cd-induced activation of Erk1/2 and JNK, as well as cell death. Cd-induced ROS was also linked to the activation of caspase-3. Pretreatment with inhibitors of JNK (SP600125) and Erk1/2 (U0126) partially blocked Cd-induced cleavage of caspase-3 and prevented cell death. However, zVAD-fmk, a pan caspase inhibitor, only partially prevented Cd-induced apoptosis. The results indicate that Cd induction of ROS inhibits PP2A and PP5, leading to activation of JNK and Erk1/2 pathways, and consequently resulting in caspase-dependent and -independent apoptosis of neuronal cells. The findings strongly suggest that the inhibitors of JNK, Erk1/2, or antioxidants may be exploited for prevention of Cd-induced neurodegenerative diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 45, Issue 7, 1 October 2008, Pages 1035-1044
Journal: Free Radical Biology and Medicine - Volume 45, Issue 7, 1 October 2008, Pages 1035-1044
نویسندگان
Long Chen, Lei Liu, Shile Huang,