Nitrotyrosine-modified SERCA2: a cellular sensor of reactive nitrogen species

作者：Bigelow Diana J^*

来源：Pflugers Archiv-European Journal of Physiology, 2009, 457(3): 701-710.

DOI：10.1007/s00424-007-0429-6

• SERCA2
• Aging
• Oxidation
• Inflammation
• Reactive oxygen species
• Nitrotyrosine

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.

• 出版日期2009-1