Open AccessAntisense-Inhibition of Plasma Membrane Ca2+ Pump Induces Apoptosis in Vascular Smooth Muscle Cells
Author(s) -
Satoshi Sasamura,
KenIchi Furukawa,
Miwa Shiratori,
Shigeru Motomura,
Yasushi Ohizumi
Publication year - 2002
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.90.164
Subject(s) - apoptosis , vascular smooth muscle , microbiology and biotechnology , chemistry , smooth muscle , membrane , biology , endocrinology , biochemistry
The effect of antisense oligodeoxynucleotides (ODNs) of plasma membrane Ca(2+)-pumping ATPase (PMCA) on rat aortic vascular smooth muscle cells (VSMCs) in primary culture was examined. More than 80% of the PMCA expressed in cultured VSMCs was the PMCA-1B subtype. Exposed to antisense ODNs against PMCA-1, not only the expression of the PMCA protein but also mRNA of PMCA-1B was diminished in a concentration-dependent manner. Extracellular Na(+)-independent (45)Ca(2+) efflux catalyzed via PMCA was inhibited with antisense ODNs. Both the resting and ionomycin- or ATP-stimulated levels of intracellular Ca(2+) were increased by antisense ODNs. Furthermore, prolonged treatment with antisense ODNs caused apoptosis in VSMCs. The occurrence of apoptosis was inhibited by FK506, a potent immunosuppressant. These results demonstrate that the PMCA was specifically inhibited by antisense ODNs and suggest that PMCA plays an important role in regulation of intracellular Ca(2+) concentrations, especially at the resting condition to prevent an occurrence of apoptosis that may be induced through the activation of calcineurin.