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G Petrosillo

Publications and source records attributed to G Petrosillo.

11 recordsLinked to original sources
PubMed1998

Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations.

Rat heart mitochondrial membranes exposed to the free radicals generating system tert-butylhydroperoxide/Cu2+ undergo lipid peroxidation as evidenced by the accumulation of thyobarbituric acid reactive substances. Mitochondrial lipid peroxidation resulted in a marked loss of both cytochrome c oxidase activity and cardiolipin content. The alterations in the properties of cytochrome c oxidase were confined to a decrease in the maximal activity (Vmax) with no change in the affinity (Km) with respect to the substrate cytochrome c. Various lipid soluble antioxidants could prevent the lipid peroxidation reaction and the associated loss of cytochrome c oxidase activity. External added cardiolipin but no other phospholipids, nor peroxidized cardiolipin was able to prevent the loss of cytochrome oxidase activity induced by lipid peroxidation. These results establish a close correlation between oxidative damage to cardiolipin and alterations in the cytochrome oxidase activity and may prove useful in probing molecular mechanism of free radicals induced peroxidative damage of mitochondria which has been proposed to contribute to aging and to chronic degenerative diseases.

Animals↗
PubMed1997

Alterations in carnitine-acylcarnitine translocase activity and in phospholipid composition in heart mitochondria from hypothyroid rats.

Changes in mitochondrial fatty acid metabolism may underlie the decline in cardiac function in the hypothyroid animals. The effect of hypothyroidism on fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid composition in rat heart mitochondria has been examined. Rates of mitochondrial fatty acid oxidation as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed in heart mitochondria isolated from hypothyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that the hypothyroid state affects the Vmax of this process, while having no effect on the K(m) value. Heart mitochondrial inner membrane lipid composition was significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease (by around 36%). Alterations in fatty acid pattern of mitochondrial inner membrane preparations from hypothyroid rats were also found. The effects of the hypothyroid state on fatty acids oxidation, carnitine translocase activity and phospholipid composition were completely reversed by following treatment of hypothyroid rats with thyroid hormone. A lower cardiolipin content in the mitochondrial inner membrane offers a plausible mechanism to explain the decline in the translocase activity in hypothyroidism.

Animals↗
PubMed1997

Age-dependent decline in the cytochrome c oxidase activity in rat heart mitochondria: role of cardiolipin.

Cardiolipin is a major mitochondrial membrane lipid and plays a pivotal role in mitochondrial function. We have recently suggested a possible involvement of this phospholipid in the age-linked decline of cytochrome c oxidase activity in rat heart mitochondria [G. Paradies et al. (1993) Arch. Gerontol. Geriatr. 16, 263-272]. The aim of this work was to test our earlier proposal. We have investigated whether addition of exogenous cardiolipin to mitochondria is able to reverse, in situ, the age-linked decrease in the cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock [Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45] was employed in order to enrich the mitochondria cardiolipin content. We demonstrate that the lower cytochrome c oxidase activity in heart mitochondria from aged rats can be fully restored to the level of young control rats by exogenously added cardiolipin. No restoration was obtained with other phospholipids or with peroxidized cardiolipin. Our data support a key role for cardiolipin in the age-linked decline of rat heart mitochondrial cytochrome c oxidase activity.

Aging↗
PubMed1997

Cardiolipin-dependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats.

Cardiolipin plays an important role in mitochondrial membrane structure and function. We have recently reported a decrease in the cytochrome c oxidase activity in heart mitochondria from hypothyroid rats (G. Paradies et al. (1993) Arch. Biochem Biophys. 307, 91-95). A possible involvement of cardiolipin in such a decrease has been proposed. The aim of this work was to test our earlier proposal. We have investigated whether addition of exogenous cardiolipin to hypothyroid mitochondria is able to reverse, in situ, their decreased cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock (Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45) was employed in order to enrich the mitochondrial cardiolipin content. We demonstrate that the decreased activity of this enzyme complex in heart mitochondria from hypothyroid rats can be completely restored to the level of control rats by exogenously added cardiolipin but not by other phospholipids. These data provide strong evidence for the involvement of cardiolipin in the thyroid hormone induced changes of mitochondrial cytochrome oxidase activity.

Animals↗
PubMed1996

Stimulation of carnitine acylcarnitine translocase activity in heart mitochondria from hyperthyroid rats.

The effect of hyperthyroidism on fatty acid oxidation and on carnitine-acylcarnitine translocase activity in rat heart mitochondria has been studied. The rates of palmitoylcarnitine supported respiration as well as the carnitine-palmitoylcarnitine exchange reaction were both stimulated (approx. 36%) in heart mitochondria from hyperthyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that thyroid hormone affects the Vmax of this process, while having no effect on the Km values. The level of cardiolipin was significantly higher (approx. 40%) in heart mitoplasts from hyperthyroid rats than from the control rats. It can be concluded that thyroid hormones produce a stimulation of heart mitochondrial carnitine translocase activity and that the basis of this effect is likely an increase in the cardiolipin content.

Animals↗
PubMed1995

Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine.

Age-related changes in mitochondrial fatty acids metabolism may underlie the progressive decline in cardiac function. The effect of aging and acute treatment with acetyl-L-carnitine on fatty acids oxidation and on carnitine-acylcarnitine translocase activity in rat heart mitochondria was studied. Rates of palmitoylcarnitine supported respiration as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed (approx. 35%) in heart mitochondria from aged rats. These effects were almost completely reversed following treatment of aged rats with acetyl-L-carnitine. Heart mitochondrial cardiolipin content was significantly reduced (approx. 38%) in aged rats. Treatment of aged rats with acetyl-L-carnitine restored the level of cardiolipin to that of young rats. It is suggested that acetyl-L-carnitine is able to reverse age-related decrement in mitochondrial carnitine-acylcarnitine exchange activity by restoring the normal cardiolipin content.

Acetylcarnitine↗
PubMed1994

Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria.

The effect of aging and treatment with acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria was studied. It was found that the activity of both these mitochondrial protein systems was reduced (by around 30%) in aged animals. Treatment of aged rats with acetyl-L-carnitine almost completely reversed this effect. Changes in the mitochondrial cardiolipin content appear to be responsible for these effects of acetyl-L-carnitine.

Acetylcarnitine↗
PubMed1994

Enhanced cytochrome oxidase activity and modification of lipids in heart mitochondria from hyperthyroid rats.

In order to further investigate the mechanism regulating the control of mitochondrial respiration by thyroid hormones, the effect of the hyperthyroidism on the kinetic characteristics of cytochrome c oxidase in rat heart mitochondria was studied. Mitochondrial preparations from both control and hyperthyroid rats had equivalent Km values for cytochrome c, while the maximal activity of cytochrome oxidase was significantly increased (by around 30%) in mitochondrial preparation from hyperthyroid rats. This enhanced activity of cytochrome oxidase was associated to a parallel increase in mitochondrial State 3 respiration. The hormone treatment resulted in a decrease in the flux control coefficient of the oxidase. The enhanced activity of cytochrome oxidase in hyperthyroid rats does not appear to be dependent on an increase in the mass of this enzyme complex in that the heme aa3 content was equivalent in both hyperthyroid and control preparations. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hyperthyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a lower temperature. Cardiolipin content was significantly increased in mitochondrial preparations from hyperthyroid rats, while there were no significant alterations in the fatty acid composition of cardiolipin of control and hyperthyroid preparations. The results support the conclusion that the enhanced cytochrome oxidase activity in heart mitochondrial preparations from hyperthyroid rats is due to a specific increase in the content of cardiolipin.

Animals↗
PubMed1993

Decreased cytochrome oxidase activity and changes in phospholipids in heart mitochondria from hypothyroid rats.

The effect of hypothyroidism on kinetic characteristics of cytochrome oxidase in rat heart mitochondria was studied. Mitochondrial preparations from control and hypothyroid rats had equivalent Km values for cytochrome c, while the maximal activity of the oxidase was significantly decreased (more than 30%) in mitochondrial preparations from hypothyroid rats. This decrease is associated to a parallel decrease in state 3 respiration. The cytochrome aa3 content was slightly decreased (by around 15%) in mitochondria from hypothyroid rats. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hypothyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a higher temperature. Cardiolipin content was markedly decreased in the mitochondrial membrane from hypothyroid rats. No alterations were found in the pattern of cardiolipin fatty acid distribution of mitochondrial membrane from control and hypothyroid rats. The effects of the hypothyroid state on the activity of cytochrome oxidase, on cytochrome aa3 levels, and on cardiolipin contents were completely reversed by following the treatment of hypothyroid rats with thyroid hormone. The results support the conclusion that the depressed mitochondrial cytochrome oxidase activity in the hypothyroid state is due, at least in part, to a decrease in the cardiolipin content of the mitochondrial inner membrane.

Animals↗