原创力文档role of trpm2 in h2o2-induced cell apoptosis in endothelial cells角色的trpm2 h2o2-induced细胞在内皮细胞凋亡.pdfVIP
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role of trpm2 in h2o2-induced cell apoptosis in endothelial cells角色的trpm2 h2o2-induced细胞在内皮细胞凋亡
Role of TRPM2 in H O -Induced Cell Apoptosis in
2 2
Endothelial Cells
1 1 1 2 1 1
Lei Sun , Ho-Yan Yau , Wei-Yan Wong , Ronald A Li , Yu Huang , Xiaoqiang Yao *
1 Li Ka Shing Institute of Health Sciences and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China, 2 Stem Cell and Regenerative
Medicine Consortium, The University of Hong Kong, Hong Kong, China
Abstract
Melastatin-like transient receptor potential channel 2 (TRPM2) is an oxidant-sensitive and cationic non-selective channel that
is expressed in mammalian vascular endothelium. Here we investigated the functional role of TRPM2 channels in hydrogen
peroxide (H O )-induced cytosolic Ca2+ ([Ca2+] ) elavation, whole-cell current increase, and apoptotic cell death in murine
2 2 i
heart microvessel endothelial cell line H5V. A TRPM2 blocking antibody (TM2E3), which targets the E3 region near the ion
permeation pore of TRPM2, was developed. Treatment of H5V cells with TM2E3 reduced the [Ca2+]i rise and whole-cell
current change in response to H O . Suppressing TRPM2 expression using TRPM2-specific short hairpin RNA (shRNA) had
2 2
similar inhibitory effect. H O -induced apoptotic cell death in H5V cells was examined using MTT assay, DNA ladder
2 2
formation analysis, and DAPI-based nuclear DNA condensation assay. Based on these assays, TM2E3 and TRPM2-specific
shRNA both showed protective effect against H O -induced apoptotic cell death. TM2E3 and TRPM2-specific shRNA also
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