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- 2017.1
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Cyclic ADP-ribose (cADPR) releases Ca2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca2+ ([Ca2+]i) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosinedephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.
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참고문헌 (25)
참고문헌 신청
Bers DM / 2002 / Cardiac excitation-contraction coupling / Nature 415 : 198 ~ 205
Cui Y / 1999 / Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle / Biochem J 342 (Pt 2) :
Dargie PJ / 1990 / Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose an
Davis BA / 1983 / Regulation of cardiac sarcoplasmic reticulum calcium transport by calcium-calmodulindependent phosphorylation / J Biol Chem 258 : 13587 ~ 13591
Eisner DA / 2004 / Sodium calcium exchange in the heart: necessity or luxury? / Circ Res 95 : 549 ~ 551
Cui Y / 1999 / Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle / Biochem J 342 (Pt 2) :
Dargie PJ / 1990 / Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose an
Davis BA / 1983 / Regulation of cardiac sarcoplasmic reticulum calcium transport by calcium-calmodulindependent phosphorylation / J Biol Chem 258 : 13587 ~ 13591
Eisner DA / 2004 / Sodium calcium exchange in the heart: necessity or luxury? / Circ Res 95 : 549 ~ 551
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