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
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:
https://lup.lub.lu.se/record/1511897
- author
- Tan, Chanyuan
LU
; Salehi, S Albert
LU
; Svensson, Siv
LU
; Olde, Björn
LU
and Erlinge, David
LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cellular and Molecular Life Sciences
- volume
- 67
- pages
- 445 - 453
- publisher
- Birkhäuser
- external identifiers
-
- wos:000273351900009
- pmid:19915796
- scopus:75849146873
- pmid:19915796
- 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
- 2016-04-04 09:44:39
- date last changed
- 2024-02-11 15:11:52
@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 = {{Birkhäuser}},
series = {{Cellular and Molecular Life Sciences}},
title = {{ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.}},
url = {{http://dx.doi.org/10.1007/s00018-009-0191-3}},
doi = {{10.1007/s00018-009-0191-3}},
volume = {{67}},
year = {{2010}},
}