H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the β-cells: involvement of TRPM2 channels
Muhammad R. Bari
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorSanian Akbar
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorMohamed Eweida
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorFrank J.P. Kühn
Institute of Physiology, Medical Faculty, University hospital RWTH, Aachen, Germany
Search for more papers by this authorAmanda Jabin Gustafsson
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorAndreas Lückhoff
Institute of Physiology, Medical Faculty, University hospital RWTH, Aachen, Germany
Search for more papers by this authorCorresponding Author
Md. Shahidul Islam
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Uppsala University Hospital, AR division, Uppsala, Sweden
Correspondence to: Md. Shahidul ISLAM, Karolinska Institutet, Department of Clinical Sciences and Education, Stockholm South Hospital, S-118 83 Stockholm, Sweden.Tel.: +46 702593446Fax: +46 76163287E-mail: [email protected]Search for more papers by this authorMuhammad R. Bari
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorSanian Akbar
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorMohamed Eweida
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorFrank J.P. Kühn
Institute of Physiology, Medical Faculty, University hospital RWTH, Aachen, Germany
Search for more papers by this authorAmanda Jabin Gustafsson
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Search for more papers by this authorAndreas Lückhoff
Institute of Physiology, Medical Faculty, University hospital RWTH, Aachen, Germany
Search for more papers by this authorCorresponding Author
Md. Shahidul Islam
Karolinska Institutet, Department of Clinical Sciences and Education, Research Centre, Stockholm South Hospital, Stockholm, Sweden
Uppsala University Hospital, AR division, Uppsala, Sweden
Correspondence to: Md. Shahidul ISLAM, Karolinska Institutet, Department of Clinical Sciences and Education, Stockholm South Hospital, S-118 83 Stockholm, Sweden.Tel.: +46 702593446Fax: +46 76163287E-mail: [email protected]Search for more papers by this authorAbstract
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 β-cells, and in human β-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 β-cells, a process potently inhibited by ACA.
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