کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10739649 | 1046883 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
β-Amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase-NF-κB signaling pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Inflammatory cell death as well as oxidative stress has been implicated in some neurodegenerative disorders such as Alzheimer's disease (AD). Expression of cyclooxygenase-2 (COX-2) and production of prostaglandins have been frequently elevated in AD. In this study, we have investigated the molecular mechanisms underlying inflammatory cell death induced by β-amyloid (Aβ), a neurotoxic peptide that accumulates in senile plaques formed in the brains of AD patients. Rat pheochromocytoma (PC12) cells treated with Aβ exhibited increased mRNA and protein expression of COX-2 and production of prostaglandin E2 (PGE2) and underwent apoptotic death as determined by positive in situ terminal end-labeling, decreased mitochondrial membrane potential, increased Bax/Bcl-XL ratio, activation of c-Jun N-terminal kinase, and cleavage of poly(ADP-ribose)polymerase. Pretreatment with celecoxib, a selective COX-2 inhibitor, attenuated Aβ-induced cell death, which was aggravated by addition of the COX-2 product PGE2. Aβ transiently induced activation of redox-sensitive transcription factor NF-κB, and pretreatment of PC12 cells with NF-κB inhibitors abolished the Aβ-induced COX-2 expression. Pharmacologic inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) and dominant-negative mutation of both enzymes suppressed not only Aβ-induced NF-κB transactivation but also COX-2 expression and PGE2 production. The above findings suggest that Aβ-induced apoptosis in PC12 cells is associated with COX-2 up-regulation through activation of NF-κB, which is mediated by upstream kinases including ERK and p38 MAPK.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 38, Issue 12, 15 June 2005, Pages 1604-1613
Journal: Free Radical Biology and Medicine - Volume 38, Issue 12, 15 June 2005, Pages 1604-1613
نویسندگان
Jung-Hee Jang, Young-Joon Surh,