Ca overload and the action of calcium sensitive proteases, phospholipases and prostaglandin E2 in myocardial cell degradation.
The mechanism of Ca overload-induced myocardial cell injury under hypoxia was examined for the involvement of calcium-activated neutral proteases (CANP), calcium-dependent phospholipases (CDP) or prostaglandins with measuring 45Ca entry, intake of biologically inert dye, nigrosin, into the cultured myocytes, as was useful for the quantification of sarcolemma permeability, and the release of creatine phosphokinase (CPK) to the culture medium. A Ca channel blocker, verapamil (1 and 10 micrograms/ml) or a Ca ionophore, A23187 (0.5 to 4 micrograms/ml) dose-dependently decreased or increased both the Ca entry and nigrosin intake in accordance with the CPK release. Furthermore, the inhibitors against CANP, NCO-700 (2 and 20 micrograms/ml) that was demonstrated to permeate sarcolemma using 14C-labelled reagent, against CDP, mepacrine (1 and 10 micrograms/ml) or against cyclooxygenase, indomethacin (1 and 10 micrograms/ml) caused no effect on the Ca entry, nigrosin intake nor CPK release under hypoxia. These results suggest that the Ca overdose into the myocardial cells potentiates their injury and it is not primarily related to the activation of CANP, CDP nor cyclooxygenase.
Toyo-oka
T
T
Hara
K
K
Nakamura
N
N
Kitahara
M
M
Masaki
T
T
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002154:Calpain; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003327:Coronary Disease / Q000201:enzymology*; D003402:Creatine Kinase / Q000378:metabolism; D015232:Dinoprostone; D010450:Endopeptidases / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010101:Oxygen Consumption / Q000187:drug effects; D010740:Phospholipases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000814:Aniline Compounds; D011458:Prostaglandins E; D000001:Calcimycin; C002712:nigrosin; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D003402:Creatine Kinase; D010740:Phospholipases; D010450:Endopeptidases; D002154:Calpain; D015232:Dinoprostone; D002118:Calcium