PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Mitochondrial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed1980

Mitochondrial function following chronic ethanol treatment: effect of diet.

Rats were fed liquid diets containing 36% of the calories as ethanol either in a high fat, adequate protein or in a high protein, low fat diet, with pair-fed controls receiving an isocaloric amount of sucrose replacing ethanol. Liver mitochondria were isolated in a fatty acid free albumin containing medium. Mitochondrial respiration respiratory control and ADP/O ratios were measured either using a glutamate-malate mixture or succinate. In rats fed the high fat adequate protein diet chronic ethanol treatment resulted in a reduction in the respiratory rates in states 3 and 4 with both substrates. However, such changes did not occur in rats fed high protein low fat diets. Using the NAD-linked substrates, but not with succinate, the respiratory control ratio was significantly decreased following ethanol treatment with the high fat adequate protein but not the high protein low fat diet. ADP/O ratios were not affected by the ethanol treatment with either diet. Ethanol metabolism rate increased by 70% in rats treated with ethanol containing high protein low fat diets and by 50% with ethanol containing high fat adequate protein diets.

Alcoholism↗
PubMed1992

Modulation of rat olfactory bulb mitochondrial function by atrial natriuretic peptide.

Atrial Natriuretic Peptide (ANP) and receptors for ANP are widely distributed in many tissues and cell types in vertebrates. ANP has been shown to be internalized into the cytoplasm in several cell types and thus it raises the possibility that it may act on intracellular receptors. Displacement experiments of [125I]-ANP binding to rat olfactory bulb mitochondrial fraction demonstrated the presence of high affinity (Kd < 10(-9)M) binding sites (Bmax, 112 fmol/mg protein) in this preparation. The addition of ANP (10(-8) M) to this mitochondrial preparation resulted in a 25% increase in TPP+ accumulation, signifying a striking hyperpolarization of the mitochondrial membrane. In contrast ANP did not increase TPP+ uptake to liver mitochondrial preparations. This direct effect of ANP on Olfactory bulb mitochondrial membrane potential may underly the known effects of this hormone on steroidogenesis.

Animals↗
PubMed1988

[Experimental study on lipid metabolism after partial hepatectomy--with reference to mitochondrial function of the regenerating liver].

Lipid metabolism after hepatectomy was studied in normal rats and cirrhotic rats induced with injections of thioacetamide. In normal rats, the fat accumulation in regenerating livers was observed, which had a maximal peak at 24 hours after hepatectomy. It could be a result of mobilization of fatty acids from fat tissue accompanied with hyperglucagonemia after hepatectomy. Mitochondrial respiration in regenerating liver increased remarkably. Especially when palmitoylcarnitine was used as a substrate, both the respiratory index and ATP synthesis were high until 72 hours after hepatectomy. Mitochondrial carnitine palmitoyltransferase activity was also high. The increase of mitochondrial respiration with palmitoylcarnitine as a substrate was also observed in cirrhotic liver until 72 hours after hepatectomy. These results suggest that mobilization of fatty acids increases after hepatectomy and regenerating liver utilizes fatty acids as a main substrate for hepatic regeneration.

Animals↗
PubMed1987

The mechanism of acute cytotoxicity of triethylphosphine gold(I) complexes. II. Triethylphosphine gold chloride-induced alterations in mitochondrial function.

Triethylphosphine gold complexes have therapeutic activity in the treatment of rheumatoid arthritis. Many of these compounds are also highly cytotoxic in vitro to a variety of tumor and non-tumor cell lines. Triethylphosphine gold chloride (TEPAu) is highly cytotoxic to isolated rat hepatocytes at concentrations greater than 25 microM. The earliest changes that could be detected in hepatocytes included bleb formation in the plasma membrane, alterations in the morphology of mitochondria, and rapid decreases in cellular ATP and oxygen consumption. The degradation of ATP could be followed sequentially through ADP and AMP and was ultimately accounted for entirely as xanthine. The sum of adenine and xanthine-derived nucleotides remained constant throughout the experiments. TEPAu (50 microM) caused a significant decrease in the hepatocyte ATP/ADP ratio and energy charge within 5 min. The antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD), which blocked TEPAu-induced malondialdehyde formation but not cell death, also had no effect on the decreases in oxygen consumption, ATP, ATP/ADP ratio, or energy charge. In isolated rat liver mitochondria, TEPAu (1 microM) caused significant reductions in carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP) (uncoupled)-stimulated respiration. TEPAu (5 microM) inhibited state 3 respiration and the respiratory control ratio without affecting state 4 respiration and caused a rapid dissipation of the mitochondrial-membrane hydrogen-ion gradient (membrane potential). Concentrations greater than 5 microM also inhibited state 4 respiration. TEPAu caused a concentration-dependent inhibition of FCCP-stimulated respiration with pyruvate/malate and succinate as substrates but had not effect on ascorbate/tetramethyl-p-phenylenediamine-supported respiration. The inhibition of state 4 respiration and FCCP-stimulated respiration by TEPAu (10 microM) could be reversed by the addition of 2 mM dithiothreitol. Dithiothreitol also partially protected cells from TEPAu-induced injury and reversed the TEPAu-induced depletion in cellular ATP. These data indicate that TEPAu may be acting functionally as a respiratory site II inhibitor, similar to antimycin. The reversal of TEPAu-induced inhibition of mitochondrial respiration and cell lethality by dithiothreitol suggests that mitochondrial thiols may be involved.

Adenosine Triphosphate↗
PubMed1975

Effect of coumarins on mitochondrial function I. Uncoupling of oxidative phosphorlation.

8-Acetyl-5,7-diemthoxy-4-phenylcoumarin at concentrations 0.03 to 0.3 mM uncoupled oxidative phosphorylation, in vitro, in rat liver mitochondria. Preincubation of mitochondria with the compound enhanced this effct. Similar uncoupling was observed with 5,7-dihydroxy-4phenylcoumarin; 7-acetonyloxycoumarin; 6,7-dimethyl-4-phenylcoumarin and 4-phenyldaphentin also. All these compounds stimulated mitochondrial ATPase activity three- to eight-fold. However, coumarin, the paretn substance of all these compounds had no effect on oxidative phosphorylation in mitochondria.

Adenosine Diphosphate↗
PubMed1991

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine on Trypanosoma cruzi.

The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes of Trypanosoma cruzi, at concentrations lower than 100 microM, and motility and infectivity of the bloodstream trypomastigote form at 200 microM. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 microM TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.

Adenosine Triphosphatases↗
PubMed2005

Mitochondrial function in schimke-immunoosseous dysplasia.

Schimke-immunoosseous dysplasia (SIOD) is a multisystemic disorder caused by a mutation of a putative chromatin remodelling protein. Spondyloepiphyseal dysplasia with disproportionate growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, defective cellular immunity, and transient ischemic attacks are major clinical features in the severe form of SIOD. In the present study we tested the hypothesis that mitochondrial dysfunction may be an underlying pathophysiologic mechanism in this multisystemic disease. Mitochondrial parameters were studied in blood (lactate, pyruvate, ketone bodies, alanine) and in urine (organic acids) of four patients with the severe form of SIOD. Activities of respiratory chain enzymes were measured spectrophotometrically in fibroblasts of two of these patients. In patients with the severe form of SIOD normal concentrations of lactate as well as normal lactate/pyruvate- and ketone-body ratios were found in plasma. Alanine, the long-term parameter for lactate, was normal as well; metabolites of the citrate cycle were not found in the urine. Activities of respiratory chain enzymes I-V were not significantly reduced in fibroblasts from two patients with the severe form of SIOD. There was no evidence for mitochondrial dysfunction in SIOD. The underlying pathophysiology of SIOD remains unclear.

Arteriosclerosis↗
PubMed2006

Sphingosine impairs mitochondrial function by opening permeability transition pore.

Growing evidence suggest that, in the heart, sphingosine participates to contractile dysfunction by altering calcium transients and mitochondria function. However, mechanisms underlying sphingosine-induced cardiac mitochondria dysfunction are poorly understood. Here, we studied the effects of sphingosine on isolated cardiac mitochondria of either wild-type or Bcl-2 overexpressing transgenic mice. Sphingosine induced reductions in ADP-coupled respiration, membrane potential, mitochondrial cytochrome c content and ATP production, which were partially prevented by cyclosporine A and mitochondrial Bcl-2 overexpression. These data suggest that sphingosine promotes mitochondrial permeability transition pore opening, which may result in uncoupled respiration and participate in cardiac contractile dysfunction.

Animals↗
PubMed1990

ATP-sensitive K+ channels reveal the effects of intracellular chloride variations on cytoplasmic ATP concentrations and mitochondrial function.

Replacement of intracellular Cl- by impermeant anions, as well as treatment of insulinoma cells by the Cl- channel blocker, NPPB, leads to activation of ATP-dependent K+ (KATP) channels. Activation of KATP channels by C1- substitution is eliminated (i) when intracellular ATP is replaced by non-hydrolyzable ATP analogs, (ii) when the perfusion medium contains an ATP regenerating system, (iii) when the mitochondrial ATPase is blocked by oligomycin. Dinitrophenol and GDP have the same activating effects on KATP channels as NPPB or intracellular Cl- substitution. Our interpretation of the results is that NPPB and intracellular Cl- replacement produce an uncoupling of oxidative phosphorylation by acting on mitochondrial anion channels, which leads to rapid degradation of ATP and to activation of KATP channels. KATP channels are useful sensors of cytoplasmic ATP variations.

Adenosine Triphosphate↗
PubMed2003

Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: implications for neuroprotection/neurodegeneration?

Primary culture rat astrocytes exposed to the long acting nitric oxide donor (Z)-1-[2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) for 24 h approximately double their concentration of glutathione (GSH) and show no sign of cell death. In contrast, GSH was depleted by 48%, and significant loss of mitochondrial respiratory chain complex activity and cell death were observed in primary culture rat neurones subjected to DETA-NO for 18 h. Northern blot analysis suggested that mRNA amounts of both subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis, were elevated in astrocytes following nitric oxide (NO) exposure. This correlated with an increase in astrocytic GCL activity. Neurones on the other hand did not exhibit increased GCL activity when exposed to NO. In addition, the rate of GSH efflux was doubled and gamma-glutamyltranspeptidase (gamma-GT) activity was increased by 42% in astrocytes treated with NO for 24 h. These results suggest that astrocytes, but not neurones, up-regulate GSH synthesis as a defence mechanism against excess NO. It is possible that the increased rate of GSH release and activity of gamma-GT in astrocytes may have important implications for neuroprotection in vivo by optimizing the supply of GSH precursors to neurones in close proximity.

Animals↗
PubMed1994

Method for recovering ATP content and mitochondrial function after chemical anoxia in renal cell cultures.

Cultured renal cells provide a highly reproducible and malleable model to study cellular responses to metabolic perturbations. Nevertheless, there is currently no good method to achieve metabolic inhibition and complete recovery in cultured cells. This study describes a specific method for reversibly inhibiting both glycolytic and oxidative metabolism. Glycolysis was inhibited by removing all glycolytic substrates, and mitochondrial respiration was inhibited with rotenone, a site I inhibitor of the electron transport chain. Within 30 min, ATP values were decreased by 98%. Glycolysis was restored through the reintroduction of glucose. Oxidative metabolism was restored by the addition of heptanoate, a short odd-chain fatty acid, which supplies reducing equivalents to site II of the electron transport chain. Employing Madin-Darby canine kidney and LLC-PK1 cell lines, this protocol caused the immediate and complete recovery of mitochondrial respiration and, by 60 min, the complete recovery of cellular ATP levels. Application of this protocol should allow the investigation of the cellular effects and alterations that occur within cells recovering from sublethal energy depletion.

Adenosine Triphosphate↗
PubMed1987

Inhibition of mitochondrial functions by margosa oil: possible implications in the pathogenesis of Reye's syndrome.

Margosa oil (MO), a fatty acid-rich extract of the seeds of the neem tree and a reported cause of Reye's syndrome, has been used in the induction of an experimental model of Reye's syndrome in rats. It has been reported that MO causes a decrease in in vivo mitochondrial enzyme activity similar to that seen in Reye's syndrome. We have attempted to uncover some of the biochemical mechanisms of MO's toxicity by examining its effect in vitro on isolated rat liver mitochondria. Male rat liver mitochondria were isolated by centrifugation; oxygen uptake, reduced forms of cytochrome b, c + c1, a + a3, and flavoprotein, intramitochondrial concentrations of acetyl coA, acid-soluble coA, acid-insoluble coA, and ATP content were measured after incubation with and without MO. Our results reveal that MO is a mitochondrial uncoupler. State 4 respiration was increased while the respiratory control ratio was decreased. The intramitochondrial content of ATP was also decreased. There were substantial changes in the reduction of the respiratory chain components after incubation of mitochondria with MO. This decelerative effect on mitochondrial electron transport was alleviated by the addition of coenzyme Q and/or carnitine. These effects of MO on mitochondrial respiration may be due to changes in fatty acid metabolism caused by MO as MO caused a shift in the proportion of acid-soluble or acid-insoluble coA esters. Supplementary therapy with L-carnitine and coenzyme Q may be useful in the management of MO-induced Reye's syndrome.

Animals↗
PubMed1986

Oxygen dependence of mitochondrial function in isolated rat cardiac myocytes.

The O2 dependence of respiratory functions was studied in suspensions of isolated rat cardiac myocytes. Direct optical spectroscopy of the oxidation of cytochromes and oxygenation of Mb showed that cytochrome alpha 3 oxidation measured at 445-460 nm parallels Mb oxygenation; half-maximal values were at 8.0 and 8.5 microM, respectively. Thus there appears to be a close functional relationship between these components in the cells. The values are very high relative to comparable values for cytochrome alpha 3 oxidation in isolated rat heart mitochondria under state 3 conditions (0.43 microM) and isolated rat heart Mb (2.8 microM). Moreover, the measured values for half-maximal oxidation of cytochromes and oxygenation of Mb in the cells are sensitive to factors that alter the O2 consumption rate of the cells. These results indicate that mitochondrial respiration results in establishment of a gradient of O2 concentration from the suspending medium to the mitochondrial inner membrane. A portion of this gradient is between the suspending medium and the region occupied by Mb, and the remainder is between the region occupied by Mb and the inner mitochondrial membrane. The intracellular O2 gradient is an important factor in determining the O2 dependence of mitochondria in cells and hence may contribute to the O2 dependence of cardiac myocyte function in vivo.

Animals↗
PubMed1997

Amelioration of mitochondrial function by a novel antioxidant U-101033E following traumatic brain injury in rats.

In the present study, a severe traumatic brain injury (TBI) was produced over the right parietal cortex of rats using the controlled cortical impact injury (CCII) model. TBI perturbed calcium homeostasis and impaired electron transfer and energy coupling activities of forebrain mitochondria isolated from injured hemispheres with a maximal injury at 12-72 h. Efficacy of the blood-brain barrier penetrating antioxidant U-101033E on TBI-induced mitochondrial impairment was evaluated. In the dose-response experiment, two i.v. boluses (vehicle or 1-10 mg/kg of U-101033E) were administered at 5 min and 2h post-TBI. Forebrain mitochondria from each hemisphere were examined at 12 h post-injury. With respect to forebrain mitochondrial dysfunction, the drug showed a bell-shaped dose-response curve with an optimal dose of 3 mg/kg (n = 5, p < 0.05 vs. vehicle). In the time-course experiment, two i.v. boluses of 3 mg U-101033E/kg (the optimal dose) were given at 5 min and 2 h post-injury and forebrain mitochondria were examined at 6 h-14 days post-injury. U-101033E significantly restored electron transfer, energy coupling capacity, and Ca2+ transport capacity during 6 h to 14 days post-injury. Our data indicate that the antioxidant U-101033E administered post-injury at proper dosage can effectively restore TBI-induced mitochondrial dysfunction and support the contention that oxidative stress plays an important role in the pathogenesis of TBI.

Animals↗