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H2O2-induced Ca2+ i...
H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the beta-cells : involvement of TRPM2 channels
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Bari, Muhammad R. (author)
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Akbar, Sanian (author)
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Eweida, Mohamed (author)
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Kühn, Frank J. P. (author)
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Gustafsson, Amanda Jabin (author)
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Lückhoff, Andreas (author)
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- Islam, M. Shahidul (author)
- Karolinska Institutet,Uppsala universitet,Medicin
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(creator_code:org_t)
- 2009-03-06
- 2009
- English.
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In: Journal of Cellular and Molecular Medicine (Print). - : Wiley. - 1582-1838 .- 1582-4934. ; 13:9B, s. 3260-3267
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Abstract
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- Type 2 melastatin-related transient receptor potential channel (TRPM2), a member of the melastatin-related TRP (transient receptor potential) subfamily is a Ca(2+)-permeable channel activated by hydrogen peroxide (H(2)O(2)). We have investigated the role of TRPM2 channels in mediating the H(2)O(2)-induced increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) in insulin-secreting cells. In fura-2 loaded INS-1E cells, a widely used model of beta-cells, and in human beta-cells, H(2)O(2) increased [Ca(2+)](i), in the presence of 3 mM glucose, by inducing Ca(2+) influx across the plasma membrane. H(2)O(2)-induced Ca(2+) influx was not blocked by nimodipine, a blocker of the L-type voltage-gated Ca(2+) 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 H(2)O(2), 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 H(2)O(2)-induced Ca(2+) entry in beta-cells, a process potently inhibited by ACA.
Keyword
- Calcium influx
- Calcium signalling
- Insulin-secreting cells
- Microfluorometry
- N-(p-amylcinnamoyl)anthranilic acid
- TRP channels
- TRPM2
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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