Biomedical subjects

V Gogvadze

Publications and source records attributed to V Gogvadze.

22 records · Page 2Linked to original sources

PubMed1994

Nitric oxide kills hepatocytes by mobilizing mitochondrial calcium.

We have recently shown (Schweizer, M., and Richter, C. (1994) Biochem. Biophys. Res. Commun. 204, 169-175) that nitric oxide (nitrogen monoxide, NO) at low concentrations potently and reversibly deenergizes isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. We now report that also in freshly prepared hepatocytes NO deenergizes mitochondria. Deenergization is reversible at low, but longer-lasting at higher NO concentrations. The drop and the recovery of the mitochondrial membrane potential are accompanied by a rise and fall of cytosolic Ca2+ levels. At higher concentrations NO kills hepatocytes. Killing is reduced when the cytosolic Ca2+ is chelated, or when the cyclic uptake and release of Ca2+ ("Ca2+ cycling") by mitochondria is prevented. We conclude that NO can kill cells by deenergizing mitochondria and thereby flooding the cytosol with Ca2+.

Animals↗

PubMed1993

Cyclosporine A protects mitochondria in an in vitro model of hypoxia/reperfusion injury.

Hypoxia/reperfusion injury is a major clinical problem. One of its hallmarks is an increased cytosolic Ca2+ content and an increased generation of reactive oxygen species in the cytosol and in mitochondria. In the present study of an in vitro model of hypoxia/reperfusion injury, mitochondria are exposed to Ca2+ in combination with extra- and intramitochondrially acting prooxidants. In this model mitochondria are damaged in a Ca(2+)-dependent manner. The extent and the site(s) of damage depend on both the kind of respiratory substrate and prooxidant used. The major damage occurs specifically at site I of the respiratory chain, and is due to hydrolysis of oxidized pyridine nucleotides and Ca2+ release followed by Ca2+ re-uptake (Ca2+ 'cycling'). Cyclosporine A completely protects against this damage. The protection is due to inhibition of pyridine nucleotide hydrolysis, an obligatory step in the sequence of events that links prooxidants to Ca2+ release from intact mitochondria.

Adenosine Diphosphate↗

PubMed1993

Thenoyltrifluoracetone induces lipid peroxidation in rat liver mitochondria.

Addition of thenoyltrifluoracetone to mitochondria oxidizing NAD-dependent substrates induced lipid peroxidation and uncoupling of oxidative phosphorylation. Butylated hydroxytoluene, an antioxidant, prevented accumulation of lipid peroxidation products but failed to prevent deenergization of the mitochondria.

Adenosine Diphosphate↗

PubMed1992

Butylated hydroxytoluene prevents cumene hydroperoxide-induced Ca2+ release from liver mitochondria by inhibiting pyridine nucleotide hydrolysis.

The mechanism by which the free radical scavenger butylated hydroxytoluene (BHT) prevents cumene hydroperoxide-induced Ca2+ release from rat liver mitochondria was studied. In Ca(2+)-loaded mitochondria cumene hydroperoxide induced a rapid oxidation and subsequent hydrolysis of the pyridine nucleotides. In the presence of BHT, pyridine nucleotide oxidation by cumene hydroperoxide occurred but was reversible as hydrolysis was prevented by BHT. However, the addition of BHT directly to rat liver submitochondrial particles did not inhibit NAD+ hydrolysis or the formation of ADP-ribose from NAD+. Thus, whilst BHT prevented NAD+ hydrolysis in isolated mitochondria, this appeared not to be due to a direct effect of BHT on the NADase. It is concluded that the mechanism of action of BHT on cumene hydroperoxide-induced Ca2+ release from mitochondria involves the inhibition of pyridine nucleotide hydrolysis by an indirect mechanism rather than the radical scavenging properties of BHT.

Adenosine Diphosphate Ribose↗