Effects of aluminum and calcium on acetyl-CoA metabolism in rat brain mitochondria.
Al complexes are known to accumulate in extra- and intracellular compartments of the brain in the course of different encephalopathies. In this study possible effects of Al accumulation in the cytoplasmic compartment on mitochondrial metabolism were investigated. Al, like Ca, inhibited pyruvate utilization as well as citrate and oxoglutarate accumulation by whole brain mitochondria. Potencies of Ca2+(total) effects were 10-20 times stronger than those of Al. Al decreased mitochondrial acetyl-CoA content in a concentration-dependent manner, along with an equivalent rise of free CoA level, whereas Ca caused loss of both intermediates from mitochondria. In the absence of Pi in the medium, Ca had no effect on mitochondrial metabolism, whereas Al lost its ability to suppress pyruvate utilization and acetyl-CoA content in Ca-free conditions. Verapamil potentiated, whereas ruthenium red reversed, Ca-evoked suppression of mitochondrial metabolism. On the other hand, in Ca-supplemented medium, Al partially overcame the inhibitory influence of verapamil. Accordingly, verapamil increased mitochondrial Ca levels much more strongly than Al. However, Al partially reversed the verapamil-evoked rise of Ca2+(total) level. These data indicate that Al accumulated in cytoplasm in the form of the Al(PO4)OH- complex may inhibit mitochondrial functions by an increase of intramitochondrial [Ca2+]total resulting from the Al-evoked rise of cytoplasmic [Ca2+]free, as well as from inhibitory interference with the verapamil binding site on the Na+/Ca2+ antiporter.
Szutowicz
A
A
Department of Clinical Biochemistry, Medical University of Gdańsk, Poland.
Bielarczyk
H
H
Kisielevski
Y
Y
Jankowska
A
A
Madziar
B
B
Tomaszewicz
M
M
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000535:Aluminum / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000032:analysis / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003470:Culture Media / Q000032:analysis; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D003470:Culture Media; D000105:Acetyl Coenzyme A; D000535:Aluminum; D002118:Calcium