Senescence marker protein-30 (SMP30) rescues cell death by enhancing plasma membrane Ca(2+)-pumping activity in Hep G2 cells.
Senescence marker protein-30 (SMP30) has been reported to decrease with aging in the rat liver. SMP30 has been also suggested to play a role as a Ca(2+)-binding protein localized in cytosol of hepatocytes. To elucidate the functional significance of SMP30, we have generated Hep G2 cell lines that stably express large amounts of SMP30 by transfection with human SMP30 cDNA. Using these cell lines, in view of the intracellular Ca2+ homeostasis, we then investigated cytosolic free Ca2+ concentration ([Ca2+]i) and Na(+)-independent Ca2+ efflux from the cells after extracellular ATP stimulation. Although stimulation of cells with ATP caused transient [Ca2+]i increase in both SMP30 and mock transfectants, rate of decrease after peak in [Ca2+]i was enhanced 2-fold by transfection of SMP30. Correspondingly, Ca2+ efflux was significantly increased in SMP30 transfectants compared with mock transfectants. In addition, more SMP30 transfectants survived than mock transfectants when cell death was induced by Ca2+ ionophore treatment. These results suggest that SMP30 regulates [Ca2+]i by modulating plasma membrane Ca(2+)-pumping activity, and thus down-regulation of SMP30 during aging may contribute to deterioration of cellular functions.
Fujita
T
T
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Japan. tofujita@center.tmig.or.jp
Inoue
H
H
Kitamura
T
T
Sato
N
N
Shimosawa
T
T
Maruyama
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D016195:G2 Phase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017136:Ion Transport; D051381:Rats; D015398:Signal Transduction; D015238:Sulfotransferases; D014162:Transfection; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513323:RGN protein, human; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D002118:Calcium