ADP receptor P2Y13 induce apoptosis in pancreatic β-cells |
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Authors: | Chanyuan Tan Albert Salehi Siv Svensson Björn Olde David Erlinge |
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Institution: | 1. Department of Cardiology, Lund University, 22185, Lund, Sweden 2. Department of Clinical Sciences, Lund University, Clinical Research Centre, 20502, Malm?, Sweden
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Abstract: | Pancreatic β-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling
in β-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y13 using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors
P2Y1 and P2Y13. Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production
by activation of P2Y1 and P2Y13, respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed
by the P2Y13 receptor antagonist MRS2211. We further discovered that blocking the P2Y13 receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in β-cell survival. These results
indicate that P2Y13 is a proapoptotic receptor in β-cells as the P2Y13 receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis. |
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