کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4011197 1602610 2013 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway
چکیده انگلیسی


• Oxidative stress induces HtrA1 production by retinal pigment epithelial cells.
• Excessive extracellular HtrA1 promotes premature senescence by activatingp38 MAPK.
• HtrA1 thus modifies the cell senescence and may cause age-related macular degeneration.

Genetic predisposition and senescence of retinal pigment epithelium induced by oxidative stress are major contributors to age-related macular degeneration (AMD). Single-nucleotide polymorphisms in HTRA1 are strongly linked to the onset of AMD. In this study, we examine the role of HtrA1 in premature senescence and cell death induced by oxidative stress. HtrA1 mRNA and protein were up-regulated during premature senescence induced by H2O2 in both mouse embryonic fibroblasts (MEFs) and ARPE-19 cells. Expression of the senescence markers p21CIP1/WAF1 and p16INK4a, and SA-β-galactosidase activity, were higher in HtrA1+/− MEFs than in HtrA1−/− MEFs. HtrA1+/+ and HtrA1+/− MEFs were more resistant than HtrA1−/− MEFs to H2O2-induced cell death. Activation of p38 MAPK by oxidative stress was quicker in HtrA1+/− MEFs than in HtrA1−/− MEFs. The effects of excess HtrA1 were examined by transient transfection of cells with HtrA1 expression vectors or by addition of recombinant proteins. Excess wild type HtrA1 accelerated premature senescence of MEFs and ARPE-19 cells, while the protease-inactive HtrA1 S328A did not. HtrA1-induced senescence was abrogated by inhibition of p38 MAPK. We conclude that HtrA1 is induced by oxidative stress and promotes premature cell senescence through p38 MAPK in a protease activity-dependent manner.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 112, July 2013, Pages 79–92
نویسندگان
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