Inhibition of pro-oxidant-induced mitochondrial pyridine nucleotide hydrolysis and calcium release by 4-hydroxynonenal.
Intra- and extra-mitochondrial Ca2+ participates in vital cellular processes. This work investigates the influence of 4-hydroxynonenal (HNE) on pro-oxidant-induced Ca2+ release from rat liver mitochondria. Ca2+ movements across the mitochondrial inner membrane, the pyridine nucleotide redox state and pyridine (nicotinamide) nucleotide hydrolysis were analysed. HNE did not influence Ca2+ uptake by mitochondria, but inhibited in a concentration-dependent manner Ca2+ release induced by t-butylhydroperoxide (tbh). Total inhibition was achieved with about 50 microM-HNE. Ca2+ release induced by the pro-oxidant alloxan was also inhibited by HNE. Oxidation of pyridine nucleotides, induced by tbh through the concerted action of glutathione peroxidase, glutathione reductase and the energy-linked transhydrogenase, was not affected by up to 50 microM-HNE. In contrast, HNE inhibited pyridine nucleotide hydrolysis in a concentration-dependent manner. The data suggest that HNE toxicity may be in part attributed to an impaired intramitochondrial Ca2+ homeostasis.
Richter
C
C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology, Zürich.
Meier
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P
D000246:Adenosine Diphosphate Ribose / Q000096:biosynthesis; D000447:Aldehydes / Q000494:pharmacology* / Q000633:toxicity; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D007424:Intracellular Fluid / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D000496:Alloxan; C027576:4-hydroxy-2-nonenal; D002118:Calcium