Sarco/endoplasmic reticulum Ca2+-pump isoform SERCA3a is more resistant tosuperoxide damage than SERCA2b

Endo/sarcoplasmic reticulum (ER) Ca2+-pumps are important for cell survival and communication but they are inactivated by reactive oxygen species (ROS ). We have previously reported that the Ca2+-pump isoform SERCA3a is more r esistant than SERCA2b to damage by peroxide. Since peroxide and superoxide differ in their redox potentials, we now report the effects of superoxide o n the two Ca2+-pump isoforms. We isolated microsomes from HEK293 cells tran siently transfected with SERCA2b or SERCA3a cDNA. We exposed these microsom es to superoxide which was generated using xanthine plus xanthine oxidase a nd catalase to prevent accumulation of peroxide due to superoxide dismutati on. Superoxide damaged the Ca2+- transport activity of both isoforms but SE RCA3a was damaged at higher concentrations of superoxide and upon longer pe riods of exposures than was SERCA2b. Thus the SERCA3a isoform is more resis tant than SERCA2b to inactivation by both superoxide and peroxide.