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Mechanism of Antiapoptotic Action of P2Y6 Receptor in Mouse Pancreatic Beta Cells
Author(s) -
Balasubramanian Ramachandran,
Jayasekara M.P. Suresh,
Jacobson Kenneth A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb585
Subject(s) - annexin , apoptosis , receptor , microbiology and biotechnology , p2y receptor , agonist , mapk/erk pathway , signal transduction , biology , chemistry , medicine , endocrinology , biochemistry
Though human pancreatic β‐cells are known to regenerate throughout adult life, type 1 and type 2 diabetic patients have a significant deficit in β‐cell mass through immune reactions and/or β‐cell apoptosis due to hyperglycemia. Therefore, new antidiabetic drugs to promote β‐cell survival as well as function are studied. P2Y 6 receptors (P2Y 6 Rs) are a class of G‐protein coupled nucleotide receptors that activate the phospholipase‐C signaling pathway. Earlier reports indicated that P2Y 6 R stimulation promotes survival of smooth muscle cells, astrocyotma cells and mouse pancreatic β‐cells against cytokine‐induced apoptosis. Here, we explore the mechanism of mouse β‐cell survival and protection by P2Y 6 R activation during apoptosis. P2Y 6 R agonist P 1 ‐(uridine 5′‐)‐P 4 ‐( N 4 ‐methoxycytidine 5′‐)triphosphate (MRS2957) significantly increased phosphorylation of MAP kinase in MIN6 cells when compared to untreated control cells. Also, changes in the expression of anti‐apoptotic proteins Bcl‐2 and Bcl‐xL were evaluated using Western blots. The cytoprotective efficacy of P2Y 6 R agonist against hydrogen peroxide‐induced apoptosis in MIN6 cells was analyzed using annexin V staining and caspase‐3 activity. The role of MAPK in P2Y 6 R action was investigated using a MAPK‐inhibitor in cells exposed to H 2 O 2 . Insight into the mechanism of antiapoptotic action mediated by P2Y 6 Rs in pancreatic β‐cells will be discussed.