Nitrotyrosine-modified SERCA2: a cellular sensor of reactive nitrogen species.
The endo-/sarcoplasmic reticulum Ca(2+)-Mg(2+)-adenosine triphosphatase (SERCA2) isoform of the sarco/endoplasmic reticulum Ca(2+)-ATPase is sensitive to cellular conditions of inflammation and oxidative stress as evidenced by the common appearance of 3-nitrotyrosine-modified forms of SERCA2 in aging and disease in both striated and smooth muscle of humans and rodent models. Structure-function studies of nitrated SERCA2 in aging heart and skeletal muscle demonstrate stoichiometric nitration of vicinal tyrosines, Tyr(294) and Tyr(295), on the lumenal side of the membrane-spanning helix, M4, which correlates with partial inhibition of Ca(2+)-ATPase activity suggesting a possible regulatory function in down-regulating mitochondrial energy production and the associated generation of reactive oxygen/nitrogen species. This review discusses recent work regarding the nitrative and oxidative sensitivity of SERCA2 in muscle with respect to general cellular mechanisms of turnover and repair of modified proteins.
Bigelow
Diana J
DJ
Cell Biology & Biochemistry, Biology Division, Pacific Northwest National Laboratory, P.O. Box 999, MS-P7-56, Richland, WA 99352, USA. diana.bigelow@pnl.gov
D000375:Aging / Q000502:physiology; D000818:Animals; D015374:Biosensing Techniques; D004734:Energy Metabolism; D006801:Humans; D008958:Models, Molecular; D009132:Muscles / Q000502:physiology; D010084:Oxidation-Reduction; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D026361:Reactive Nitrogen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases