期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 13, 期 9B, 页码 3260-3267出版社
WILEY
DOI: 10.1111/j.1582-4934.2009.00737.x
关键词
calcium influx; TRPM2; TRP channels; insulin-secreting cells; microfluorometry; N-(p-amylcinnamoyl)anthranilic acid; calcium signalling
资金
- Swedish Research Council [K2006-72X-20159-01-3]
- Karolinska Institutet, Swedish Medical Society
- Stiftelsen Irma och Arvid Larsson-Rosts minne, Stiftelsen Goljes Minne, Svenska Diabetesstiftelsen
- Juvenile Diabetes Research Foundation
- Karolinska Institutet
Type 2 melastatin-related transient receptor potential channel (TRPM2), a member of the melastatin-related TRP (transient receptor potential) subfamily is a Ca2+-permeable channel activated by hydrogen peroxide (H2O2). We have investigated the role of TRPM2 channels in mediating the H2O2-induced increase in the cytoplasmic free Ca2+ concentration ([Ca2+](i)) in insulin-secreting cells. In fura-2 loaded INS-1E cells, a widely used model of beta-cells, and in human beta-cells, H2O2 increased [Ca2+](i), in the presence of 3 mM glucose, by inducing Ca2+ influx across the plasma membrane. H2O2-induced Ca2+ influx was not blocked by nimodipine, a blocker of the L-type voltage-gated Ca2+ channels nor by 2-aminoethoxydiphenyl borate, a blocker of several TRP channels and store-operated channels, but it was completely blocked by N-(p-amylcinnamoyl)anthranilic acid (ACA), a potent inhibitor of TRPM2. Adenosine diphosphate phosphate ribose, a specific activator of TRPM2 channel and H2O2, induced inward cation currents that were blocked by ACA. Western blot using antibodies directed to the epitopes on the N-terminal and on the C-terminal parts of TRPM2 identified the full length TRPM2 (TRPM2-L), and the C-terminally truncated TRPM2 (TRPM2-S) in human islets. We conclude that functional TRPM2 channels mediate H2O2-induced Ca2+ entry in beta-cells, a process potently inhibited by ACA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据