Ca2+ release from mitochondria induces cytosolic enzyme leakage in anoxic liver.
The mechanisms of elevation of cytosolic Ca2+ concentration during anoxia causing cytosolic enzyme leakage were studied in perfused rat liver. Before anoxia the Ca2+ contents in mitochondria of perfused rat liver were varied by addition of noradrenaline and glucagon, lowering Ca2+ concentration in the perfusion medium, and addition of Ca2+ channel blocker, either singly or in combination. The amount of cytosolic enzyme leakage during anoxic perfusion positively correlated with the mitochondrial Ca2+ content just before anoxia and also with Ca2+ release from mitochondria during anoxia. However, the amount of cytosolic enzyme leakage during anoxic perfusion did not correlate with the Ca2+ concentration in the perfusion medium and microsomal Ca2+ content. These data support the hypothesis that in anoxic liver, the cytosolic Ca2+ concentration is elevated to a pathological level mainly by Ca2+ release from mitochondria, causing the cytosolic enzyme leakage.
Hatanaka
N
N
First Department of Surgery, Osaka University Medical School, Japan.
Kamike
W
W
Shimizu
S
S
Miyata
M
M
Inoue
T
T
Yoshida
Y
Y
Tagawa
K
K
Matsuda
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D007202:Indicators and Reagents; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D010477:Perfusion; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007202:Indicators and Reagents; D004533:Egtazic Acid; D010762:Phosphorylase a; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium