Phospholipase C-delta1 rescues intracellular Ca2+ overload in ischemic heart and hypoxic neonatal cardiomyocytes.
Ischemia and simulated ischemic conditions cause intracellular Ca2+ overload in the myocardium. The relationship between ischemia injury and Ca2+ overload has not been fully characterized. The aim of the present study was to investigate the expression and characteristics of PLC isozymes in myocardial infarction-induced cardiac remodeling and heart failure. In normal rat heart tissue, PLC-delta1 (about 44 ng/mg of heart tissue) was most abundant isozymes compared to PLC-gamma1 (6.8 ng/mg) and PLC-beta1 (0.4 ng/mg). In ischemic heart and hypoxic neonatal cardiomyocytes, PLC-delta1, but not PLC-beta1 and PLC-gamma1, was selectively degraded, a response that could be inhibited by the calpain inhibitor, calpastatin, and by the caspase inhibitor, zVAD-fmk. Overexpression of the PLC-delta1 in hypoxic neonatal cardiomyocytes rescued intracellular Ca2+ overload by ischemic conditions. In the border zone and scar region of infarcted myocardium, and in hypoxic neonatal cardiomyocytes, the selective degradation of PLC-delta1 by the calcium sensitive proteases may play important roles in intracellular Ca2+ regulations under the ischemic conditions. It is suggested that PLC isozyme-changes may contribute to the alterations in calcium homeostasis in myocardial ischemia.
Hwang
Ki-Chul
KC
Department of Internal Medicine, Cardiovascular Research Institute, Yonsei University College of Medicine, Yonsei University, Seoul 120-752, South Korea.
Lim
Soyeon
S
Kwon
Hyuck Moon
HM
Bae
Yun Soo
YS
Kang
Seok-Min
SM
Chung
Kwang-Hoe
KH
Graham
Robert M
RM
Rhee
Sue Goo
SG
Jang
Yangsoo
Y
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism*; D054803:Phospholipase C delta; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D010738:Type C Phospholipases; D054803:Phospholipase C delta; C518026:Plcd1 protein, rat; D002118:Calcium