A study on permeability transition pore opening and cytochrome c release from mitochondria, induced by caspase-3 in vitro.
ABSTRACT We recently described that there is a feedback amplification of cytochrome c release from mitochondria by caspases. Here we investigated how caspases impact on mitochondria to induce cytochrome c release and found that recombinant caspase-3 induced opening of permeability transition pore and reduction of membrane potential in vitro. These events were inhibited by Bcl-xL, cyclosporin A and z-VAD.fmk. Moreover, caspase-3 stimulated the rate of mitochondrial state 4 respiration, superoxide production and NAD(P)H oxidation in a Bcl-xL- and cyclosporin A-inhibitable manner. These results suggest that caspase-3 induces cytochrome c release by inducing permeability transition pore opening which is associated with changes in mitochondrial respiration and redox potential.
Article: EFFECT OF GARLIC ADMINISTRATION ON RAT HEART MITOCHONDRIAL ENZYMES AFTER NOISE STRESS EXPOSURE[show abstract] [hide abstract]
ABSTRACT: Background: Noise has been recognized as one of the risk factors for cardiovascular diseases. Garlic is one of the oldest medications used in human culture. Garlic is used in herbal medicine for thousands of years and also as one of the main food ingredient. The present study was aimed to investigate the cardioprotective effect of garlic after noise exposure in Wistar albino rats. Methods: Animals were exposed to 1 day, 15 days and 30 days of noise stress exposure. The myocardial activity was evaluated by estimating the heart mitochondrial enzymes like malate dehydrogenase, isocitrate dehydrogenase, alpha ketoglutarate dehydrogenase, NADH dehydrogenase and cytochrome C oxidase. Garlic was administered to the animals at the dosage of 125 mg/kg b.w.) Results: Exposure to 1 day, 15 days and 30 days of noise stress has significantly decreased the all the enzymic activities studied when compared with control. Supplementation of garlic (125 mg/kg b.w.) to 1 day noise stress exposed and 15 days noise stress exposed animals could not produce any significant change and it was similar to that of untreated noise exposed animals and markedly showed a decrease in all the enzyme activity from controls. However, in 30 days aqueous garlic homogenate supplementation has significantly increased all the enzyme activities from the 30 days stress exposed group but its enzymic activity still showed a marked decrease from the control animals. Conclusion: The result indicated that noise exposure affects the mitochondrial performance in the myocardium and that long-term consumption of garlic is beneficial. As garlic is already under human consumption, dietary supplementation of garlic for prolonged period may be beneficial as one could not avoid noise in the modern way of living.International journal of pharmaceutical sciences and research. 08/2012;
Article: The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction.[show abstract] [hide abstract]
ABSTRACT: Mitochondria play central roles in cellular metabolism and apoptosis and are a major source of reactive oxygen species (ROS). We investigated the role of ROS and mitochondria in radiation-induced apoptosis in multiple myeloma cells. Two distinct levels of ROS were generated following irradiation: a small increase observed early, and a pronounced late increase, associated with depletion of reduced glutathione (GSH) and collapse of mitochondrial membrane potential (deltapsi(m)). Exogenous ROS and caspase-3 induced deltapsi(m) drop and cytochrome c release from mitochondria, which could be prevented by molecular (dominant-negative caspase-9) and pharmacologic (zVAD-fmk) caspase inhibitors and overexpression of Bcl-2. Exogenous ROS also induced mitochondrial permeability transition (PT) pore opening and cytochrome c release in isolated mitochondria, which could be blocked by inhibition of PT with cyclosporin A. These results indicate that the late ROS production is associated with increased PT pore opening and decreased deltapsi(m), and GSH, events associated with caspase activation and cytochrome c release.Cell Death and Differentiation 04/2003; 10(3):323-34. · 8.85 Impact Factor