Journal
PHARMACOLOGICAL RESEARCH
Volume 58, Issue 3-4, Pages 232-239Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2008.08.004
Keywords
Ischemia; Uracil nucleotide; G protein-coupled receptor; Tumor necrosis factor; Skeletal muscle; UDP
Categories
Funding
- NIH
- National Institute of Diabetes and Digestive and Kidney Diseases
Ask authors/readers for more resources
Activation of the G(q)-coupled P2Y(6) receptor heterologously expressed in astrocytes significantly attenuates apoptosis induced by tumor necrosis factor alpha (TNF alpha). We have extended the analysis of P2Y(6) receptor-induced cytoprotection to mouse skeletal muscle cells endogenously expressing this receptor. The endogenous P2Y(6) receptor agonist UDP and synthetic agonist MRS2693 protected C2C12 skeletal muscle cells against apoptosis in a concentration-dependent manner (0.1-10 nM) as determined by propidium iodide staining, histochemical analysis using hematoxylin and Hoechst 33258, and DNA fragmentation. The insurmountable P2Y(6) receptor antagonist MRS2578 blocked the protection. TNF alpha-induced apoptosis in C2C12 cells correlated with activation of the transcription factor NF-kappa B. The NF-kappa B activation was attenuated by 10 nM MRS2693, which activated the antiapoptic ERK1/2 pathway. In an in vivo mouse hindlimb model, MRS2693 protected against skeletal muscle ischemia/reperfusion injury. The P2Y(6) receptor is a novel cytoprotective receptor that deserves further exploration in ameliorating skeletal muscle injury. (C) 2008 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available