Calcium signaling-mediated endogenous protection of cell energetics in the acutely diabetic myocardium.
In acute diabetic myocardium, calcium signals propagated by intracellular calcium transients participate in the protection of cell energetics via upregulating the formation of mitochondrial energy transition pores (ETP). Mechanisms coupling ETP formation with an increase in membrane fluidity and a decrease in transmembrane potential of the mitochondria are discussed. Our results indicate that the amplification of calcium transients in the diabetic heart is associated with an increase in their amplitude. Moreover, the signals transferred by calcium transients also regulated ETP formation in nondiabetic myocardium. Evidence for the indispensable role of calcium in the regulation of transition pore formation is provided whereby an exchange of cadmium for calcium ions led to a rapid and dramatic decrease in the amount of ETP. Another possible regulatory factor of the mitochondrial function may be radical-induced damage to the diabetic heart. Nevertheless, our data indicate that radical-induced changes in mitochondria predominantly concern the respiratory chain and have no appreciable effect on the fluidity of the mitochondrial membranes. The residual mitochondrial production of ATP owing to its augmented transfer to the cytosol proved to be adequate to preserve sufficient levels of adenine nucleotides in the acute diabetic myocardium.
Ziegelhöffer
Attila
A
Institute for Heart Research, Slovak Academy of Sciences, 840 05 Bratislava 45, Slovak Republic. usrdzigy@savba.sk
Waczulíková
Iveta
I
Ferko
Miroslav
M
Kincelová
Dana
D
Ziegelhöffer
Barbara
B
Ravingerová
Tána
T
Cagalinec
Michal
M
Schönburg
Markus
M
Ziegelhoeffer
Tibor
T
Sikurová
Libusa
L
Ulicná
Olga
O
Mujkosová
Jana
J
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D002118:Calcium