کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2596865 1132554 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
15-Deoxy-Δ12,14-prostaglandin J2 induces mitochondrial-dependent apoptosis through inhibition of PKA/NF-κB in renal proximal epithelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
15-Deoxy-Δ12,14-prostaglandin J2 induces mitochondrial-dependent apoptosis through inhibition of PKA/NF-κB in renal proximal epithelial cells
چکیده انگلیسی

We have previously reported the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces renal proximal epithelial cell death through NF-κB inhibition. However, the upstream and down-stream signaling pathways that NF-κB inhibition mediates 15d-PGJ2-induced apoptosis remain to be defined. In the present study, we determined whether NF-κB inhibition induces cell death through the mitochondrial apoptotic pathway and whether protein kinase A (PKA) functions upstream of NF-κB inhibition by 15d-PGJ2. The role of NF-κB inhibition in this apoptotic pathway was evaluated using NF-κB p65 transfected cells. 15d-PGJ2 induced cell death by a PPARγ-independent mechanism and the cell death was prevented by NF-κB p65 transfection. 15d-PGJ2 treatment caused disruption of mitochondrial membrane potential, cytochrome c release, and caspase-3 activation, suggesting that 15d-PGJ2 induces cell death through a mitochondria-dependent apoptotic mechanism. These changes by 15d-PGJ2 were attenuated by NF-κB p65 transfection. 15d-PGJ2 treatment resulted in an increase in Bax expression, which were blocked by NF-κB p65 transfection. 15d-PGJ2 treatment caused PKA inhibition and 15d-PGJ2-induced cell death was enhanced by the PKA specific inhibitor H89. Inhibition of NF-κB by 15d-PGJ2 was prevented by addition of forskolin, a PKA activator. Taken together, these results suggest that PKA-dependent NF-κB inhibition stimulates 15d-PGJ2-mediated mitochondrial apoptotic pathway through alterations in expression of the NF-κB target genes Bax.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 258, Issue 1, 5 April 2009, Pages 17–24
نویسندگان
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