ACCUMULATION OF NITROTYROSINE ON THE SERCA2A ISOFORM OF SR CA-ATPASE OF RAT SKELETAL-MUSCLE DURING AGING - A PEROXYNITRITE-MEDIATED PROCESS

The SR Ca-ATPase in skeletal muscle SR vesicles isolated from young ad ult (5 months) and aged (28 months) rats mas analyzed for nitrotyrosin e. Only the SERCA2a isoform contained significant amounts with approxi mately one and four nitrotyrosine residues per young and old Ca-ATPase , respectively. The in vitro exposure of SR vesicles of young rats to peroxynitrite yielded selective nitration of the SERCA2a Ca-ATPase eve n in the presence of excess SERCA1a. No nitration was observed during the exposure of SR vesicles to nitric oxide in the presence of O-2. Th ese data suggest the in vivo presence of peroxynitrite in skeletal mus cle, The greater nitrotyrosine content of SERCA2a from aged tissue imp lies an age-associated increase in susceptibility to oxidation by this species.