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ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.

Tan, Chanyuan LU ; Salehi, S Albert LU ; Svensson, Siv LU ; Olde, Björn LU and Erlinge, David LU (2010) In Cellular and molecular life sciences : CMLS 67. p.445-453
Abstract
Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y(1) and P2Y(13), respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y(13) receptor antagonist MRS2211. We further discovered that blocking the... (More)
Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y(1) and P2Y(13), respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y(13) receptor antagonist MRS2211. We further discovered that blocking the P2Y(13) receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in beta-cell survival. These results indicate that P2Y(13) is a proapoptotic receptor in beta-cells as the P2Y(13) receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cellular and molecular life sciences : CMLS
volume
67
pages
445 - 453
publisher
Birkhaüser
external identifiers
  • WOS:000273351900009
  • PMID:19915796
  • Scopus:75849146873
ISSN
1420-9071
DOI
10.1007/s00018-009-0191-3
language
English
LU publication?
yes
id
3681f608-2a1a-4a9e-a6a3-9380fe4ba321 (old id 1511897)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19915796?dopt=Abstract
date added to LUP
2009-12-03 14:59:25
date last changed
2017-01-08 05:36:05
@article{3681f608-2a1a-4a9e-a6a3-9380fe4ba321,
  abstract     = {Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y(1) and P2Y(13), respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y(13) receptor antagonist MRS2211. We further discovered that blocking the P2Y(13) receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in beta-cell survival. These results indicate that P2Y(13) is a proapoptotic receptor in beta-cells as the P2Y(13) receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis.},
  author       = {Tan, Chanyuan and Salehi, S Albert and Svensson, Siv and Olde, Björn and Erlinge, David},
  issn         = {1420-9071},
  language     = {eng},
  pages        = {445--453},
  publisher    = {Birkhaüser},
  series       = {Cellular and molecular life sciences : CMLS},
  title        = {ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.},
  url          = {http://dx.doi.org/10.1007/s00018-009-0191-3},
  volume       = {67},
  year         = {2010},
}