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At least 631 records · Page 35Linked to original sources
PubMed2001

Effect of the immunosuppressant drug FK506 on neonatal cerebral mitochondrial function and energy metabolism after transient intrauterine ischemia in rats.

Mitochondrial respiratory activities and energy metabolism were measured in neonatal rat brains to evaluate the influence of transient intrauterine ischemia on the near-term fetus and to assess the effect of the immunosuppressant drug FK506 treatment. Transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion at 17 days of gestation in Wistar rats. The vehicle or 1.0 mg/kg of FK506 was administered after 1 h of recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and samples of cerebral cortical tissue were obtained from pups at 1 h after birth. The mitochondrial respiration was measured polarographically in homogenates. For the analysis of ATP, ADP, and AMP, neonatal brains were frozen in situ and fluorometric enzymatic techniques were used. In the neonatal cortical tissue exposed to ischemia, mitochondrial respiratory activities and ATP concentrations decreased significantly to approximately 59 and 67% of those in normoxic controls, respectively. The deterioration of both mitochondrial respiratory activities and high-energy phosphates was prevented by FK506, given 1 h after the start of recirculation. The present results indicate that transient intrauterine ischemia is accompanied by mitochondrial dysfunction and cellular bioenergetic failure in the neonatal rat brain and suggest that treatment with FK506 prevents the deterioration, even when administered after the ischemic periods.

Animals↗
PubMed2000

A DNA helicase required for maintenance of the functional mitochondrial genome in Saccharomyces cerevisiae.

A novel DNA helicase, a homolog of several prokaryotic helicases, including Escherichia coli Rep and UvrD proteins, is encoded by the Saccharomyces cerevisiae nuclear genome open reading frame YOL095c on the chromosome XV. Our data demonstrate that the helicase is localized in the yeast mitochondria and is loosely associated with the mitochondrial inner membrane during biochemical fractionation. The sequence of the C-terminal end of the 80-kDa helicase protein is similar to a typical N-terminal mitochondrial targeting signal; deletions and point mutations in this region abolish transport of the protein into mitochondria. The C-terminal signal sequence of the helicase targets a heterologous carrier protein into mitochondria in vivo. The purified recombinant protein can unwind duplex DNA molecules in an ATP-dependent manner. The helicase is required for the maintenance of the functional ([rho(+)]) mitochondrial genome on both fermentable and nonfermentable carbon sources. However, the helicase is not essential for the maintenance of several defective ([rho(-)]) mitochondrial genomes. We also demonstrate that the helicase is not required for transcription in mitochondria.

Amino Acid Sequence↗
PubMed1997

Mitochondrial function in muscle from elderly athletes.

The extent to which mitochondria are involved in the aging process is controversial; much of the reported decline in mitochondrial oxidations in human skeletal muscle may be due to disease and inactivity rather than age. To study true aging, mitochondrial respiratory chain function was studied in 9 young and 12 elderly athletes. No significant deterioration with age was observed. If mitochondria are involved in aging, it must be through a more subtle mechanism than a global decline in respiratory chain activity.

Adult↗
PubMed2006

[Effects of sodium nitroprusside on mitochondrial function of rye and wheat root tip under aluminum stress].

Sodium nitroprusside (SNP) could ameliorate the inhibition effect of Al on root growth of rye (Secale cereale L. cv. King) and wheat (Triticum aestivum L. cv. Jinmai47). Respiratory rate, P/O, OPR (oxygenated phosphate rate), R(3) (oxygen consumption rate with ADP and substrate present), R(4) (oxygen consumption rate with substrate) and RCR (respiratory control ratio, R(3)/R(4)) of root tips from rye and wheat decreased, as well as the activities of H(+)-ATPase, H(+)-PPase, Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase, but they increased with SNP treatment. It showed that mitochondrial respiratory functions of root tips from rye and wheat were damaged, phosphorylation was un-coupled by Al, but that of rye was less than that of wheat. Rye has high Al-resistance ability than wheat. SNP is one of donor of NO, it is suggested that NO can ameliorate remarkably respiratory dysfunction resulted from Al stress, so that NO can ameliorate the inhibition effect of Al on plant growth.

Aluminum↗
PubMed2005

Tamoxifen protects against acute tumor necrosis factor alpha-induced cardiac injury via improving mitochondrial functions.

Tamoxifen is the most commonly used antiestrogen for the treatment of breast cancer. Several clinical trials demonstrate that tamoxifen reduces the risk of heart disease and osteoporosis. However, the mechanism by which tamoxifen causes cardioprotection is unclear. Because increased levels of tumor necrosis factor alpha (TNFalpha) in tissue and/or plasma have been observed in virtually all forms of cardiac injury, we investigated whether tamoxifen prevents cardiac injury in a murine model of acute TNFalpha challenge. Five- to six-week-old female mice were injected (ip) with tamoxifen at 0.25 mg/kg daily for 3 or 7 days before receiving an injection of TNFalpha. Ultrastructural examination of cardiac tissues revealed remarkable protection against TNFalpha-induced mitochondrial damage in tamoxifen pretreated mice. Tamoxifen treatment significantly improved the mitochondrial respiratory function and enhanced superoxide-scavenging activity of mitochondria. These findings reveal a novel mitochondria-mediated mechanism by which tamoxifen exerts its cardiac protection effect against acute TNFalpha-induced heart injury.

Animals↗
PubMed1990

[Effects of levocarnitine chloride, a new mitochondrial function reactivating agent, on fatty acid and glucose oxidation under hypoxic condition in homogenates from rat heart].

The effects of levocarnitine chloride [LC-80, (-)-(R)-(3-carboxy-2-hydroxypropyl)-trimethylammonium chloride] on the oxidation of [U-14C]palmitate, [U-14C]glucose and [2-3H]glucose under hypoxic conditions in homogenates from the rat heart were investigated. LC-80 at concentrations of 0.5 and 1.0 mM caused significant and concentration-dependent increases in the depressed 14CO2 production from [U-14C]palmitate or [U-14C]-glucose oxidation under hypoxia up to 50 min after the addition of LC-80. In contrast, a marked increase in 3H2O production from [2-3H]glucose oxidation under hypoxia was observed, and LC-80 at concentrations of 0.5 and 1.0 mM caused further significant and concentration-dependent enhancement of 3H2O production up to 50 min after the addition of LC-80. Moreover, LC-80 at a concentrations of 1.0 mM significantly restored the marked depression of pyruvate dehydrogenase complex activity and mitochondrial respiratory function under hypoxia. These results suggested that LC-80 has an improving effect on myocardial metabolism under ischemia by enhancing fatty acid and glucose metabolisms.

Animals↗
PubMed2003

Differential effects of typical and atypical neuroleptics on mitochondrial function in vitro.

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 microM. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

Animals↗
PubMed1995

Muscle creatine kinase-deficient mice. II. Cardiac and skeletal muscles exhibit tissue-specific adaptation of the mitochondrial function.

Functional properties of in situ mitochondria and of mitochondrial creatine kinase were studied in saponin-skinned fibers taken from normal and M-creatine kinase-deficient mice. In control animals, apparent Km values of mitochondrial respiration for ADP in cardiac (ventricular) and slow-twitch (soleus) muscles (137 +/- 16 microM and 209 +/- 10 microM, respectively) were manyfold higher than that in fast-twitch (gastrocnemius) muscle (7.5 +/- 0.5 microM). Creatine substantially decreased the Km values only in cardiac and slow-twitch muscles (73 +/- 11 microM and 131 +/- 21 microM, respectively). As compared to control, in situ mitochondria in transgenic ventricular and slow-twitch muscles showed two times lower Km values for ADP, and the presence of creatine only slightly decreased the Km values. In mutant fast-twitch muscle, a decrease rather than increase in mitochondrial sensitivity to ADP occurred, but creatine still had no effect. Furthermore, in these muscles, relatively low oxidative capacity was considerably elevated. It is suggested that in the mutant mice, impairment of energy transport function in ventricular and slow-twitch muscles is compensated by a facilitation of adenine nucleotide transportation between mitochondria and cellular ATPases; in fast-twitch muscle, mainly energy buffering function is depressed, and that is overcome by an increase in energy-producing potential.

Adaptation, Physiological↗
PubMed2026

Relaxin-2: Shaping the Proteomic Landscape of Skeletal Muscle Physiology, Glucose Trafficking, and Mitochondrial Function in Rat.

Relaxin-2 is a hormone with robust beneficial effects on the heart and blood vessels and potential as a therapy for cardiovascular (CV) disease. Considering the interorgan communication between skeletal muscle and heart, and the relation between muscle quality/composition and CV events, we hypothesize that relaxin-2 may regulate skeletal muscle physiology and metabolism. We aim to evaluate the impact of relaxin-2 on the proteome of skeletal muscle from healthy Sprague-Dawley rats. Animals were treated with 0.4 mg/kg/day of serelaxin (recombinant form of human relaxin-2) or vehicle (PBS) for 2 weeks employing subcutaneous osmotic minipumps. Skeletal muscle protein identification and quantification were performed by LC-MS/MS using a Data-Independent Acquisition (DIA)-Sequential Window Acquisition of All Theoretical Fragment Ion Spectra (SWATH) method. SWATH/MS quantitative analysis identified that relaxin-2 significantly decreased 95 proteins and significantly increased 32 proteins in rat skeletal muscle when compared to control rats. From these, 34 proteins were associated with muscle function, myogenesis, muscle differentiation and/or regeneration, 20 are mitochondrial proteins (six from the complexes of the electron transport chain), and 10 proteins participate in glucose metabolism. Qualitative data-dependent workflow analysis identified 35 proteins exclusive to the skeletal muscle of the relaxin-2-treated group: eight proteins related to processes of skeletal muscle function (size, ion homeostasis or organization of caveolae structures and cytoskeleton) and myogenesis, and two proteins involved in muscle differentiation. Our work highlighted for the first time the role of relaxin-2 in crucial processes of muscle physiology and energetic metabolism, which could influence several processes involved in myopathy and CV.

Animals↗
PubMed1982

31P NMR studies of control of mitochondrial function in phosphofructokinase-deficient human skeletal muscle.

Metabolic control of mitochondrial respiratory activity by Pi and ADP has been evaluated by 31P NMR measurements of the levels of Pi in normal exercising human skeletal tissues in the resting-active-resting transition and, in this contribution, in the phosphofructokinase (PFK)-deficient leg. The latter studies show near constancy of Pi in the recovery from maximal exercise of the leg, with large changes of sugar phosphate (SP) complementary to the changes of phosphocreatine (PCr). The PFK deficiency permits observation of PCr resynthesis in postexercise recovery under conditions of nearly constant Pi and ATP--a phenomenon not evident in normal exercising muscle. The constancy of free Pi is inconsistent with its role in control of mitochondrial activity, leaving ADP as a key metabolic control element. These results help clarify previous controversies on the nature of control of metabolic activity of mitochondria and extend the idea of ADP control of mitochondrial metabolic states in vivo and, in addition, provide an appropriate exercise protocol for the evaluation of a genetic deficiency affecting mitochondrial metabolism.

Adenosine Diphosphate↗
PubMed1990

Ciprofloxacin does not inhibit mitochondrial functions but other antibiotics do.

At clinical concentrations, ciprofloxacin did not inhibit mitochondrial DNA replication, oxidative phosphorylation, protein synthesis, or mitochondrial mass (transmembrane potential). No difference in supercoiled forms of DNA was observed. The tetracyclines and chloramphenicol inhibited protein synthesis at clinically achievable concentrations, while rifampin, fusidic acid, and clindamycin did not.

Animals↗
PubMed1978

[Effect of melitten from bee venom on mitochondrial functions].

Effect of different concentrations of bee venom melittin on respiration, mitochondrial oxidative phosphorylation, and permeability of mitochondrial inner membranes for different ions is studied. Low melittin concentrations (1-2 mcM) increased in several times the rate of H+, K+, Na+ ions and Tris transport, in a lesser degree--bivalent ions and Cl- transport and did not affect the permeability for succrose. Thus, the uncoupling effect of low melittin concentrations on mitochondrial energetic apparatus is due to unspecific increase of inner membrane permeability. High melittin concentrations (50-100 mcM) inhibited mitochondrial respiration due to disturbances of membrane and organized respication complexes structures.

Bee Venoms↗
PubMed1995

Effects of 3,3',5-triiodo-L-thyronine (L-T3) and T3 analogues on mitochondrial function.

The effects of L-T3 and several analogues on mitochondrial parameters were determined in hypothyroid rats. These parameters include the 24 hour hormone-induced changes in the bc1 complex and in the inner membrane's proton permeability. L-T3, and all analogues except rT3, increased mitochondrial ubiquinone to euthyroid levels. L-T3, D-T3 and 3'IpT2 but not rT3, Triac, Triprop, or Dimit, altered the bypass respiration in the bc1 complex. L-T3, D-T3, Triac, 3'IpT2, and Triprop, but not rT3 or Dimit, increased the membrane's proton permeability. Actinomycin D did not prevent the increase in mitochondrial ubiquinone or the permeability change. The results show the selective thyromimetic properties of the analogues and that some of the mitochondrial changes do not require protein synthesis.

Animals↗
PubMed2006

Yeast oxidative stress response. Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state.

We investigated the changes in the oxidative stress response of yeast cells suffering mitochondrial dysfunction that could impair their viability. First, we demonstrated that cells with this dysfunction rely exclusively on cytosolic thioredoxin peroxidase I (cTPxI) and its reductant sulfiredoxin, among other antioxidant enzymes tested, to protect them against H2O2-induced death. This cTPxI-dependent protection could be related to its dual functions, as peroxidase and as molecular chaperone, suggested by mixtures of low and high molecular weight oligomeric structures of cTPxI observed in cells challenged with H2O2. We found that cTPxI deficiency leads to increased basal sulfhydryl levels and transcriptional activation of most of the H2O2-responsive genes, interpreted as an attempt by the cells to improve their antioxidant defense. On the other hand, mitochondrial dysfunction, specifically the electron transport blockage, provoked a huge depletion of sulfhydryl groups after H2O2 treatment and reduced the H2O2-mediated activation of some genes otherwise observed, impairing cell defense and viability. The transcription factors Yap1 and Skn7 are crucial for the antioxidant response of cells under inhibited electron flow condition and probably act in the same pathway of cTPxI to protect cells affected by this disorder. Yap1 cellular distribution was not affected by cTpxI deficiency and by mitochondrial dysfunction, in spite of the observed expression alterations of several Yap1-target genes, indicating alternative mechanisms of Yap1 activation/deactivation. Therefore, we propose that cTPxI is specifically important in the protection of yeast with mitochondrial dysfunction due to its functional versatility as an antioxidant, chaperone and modulator of gene expression.

Cytoplasm↗
PubMed2001

Effects of propionyl-L-carnitine on isolated mitochondrial function in the reperfused diabetic rat heart.

The effects of propionyl-L-carnitine (PLC) on isolated mitochondrial respiration in the ischemic reperfused diabetic heart were studied. Oral PLC treatment of STZ-diabetic rats was initiated for a period of 6 weeks. After treatment, isolated working hearts from diabetic rats were perfused under aerobic conditions then subjected to 25 min of no-flow ischemia followed by 15 min of aerobic reperfusion. At the end of reperfusion, heart mitochondria was isolated using differential centrifugation and respiration measured in the presence of pyruvate, glutamate, and palmitoylcarnitine. Our results indicate that diabetes was characterized by a pronounced decrease in heart function under aerobic conditions as well as during reperfusion following ischemia. Treatment with PLC resulted in a significant improvement in heart function under these conditions. The depressions in state 3 mitochondrial respiration with both pyruvate and glutamate seen in reperfused hearts from diabetic rats were prevented by PLC. State 3 respiration in the presence of palmitoylcarnitine was also improved in the ischemic reperfused diabetic rat heart. Our results show that PLC improves recovery of mechanical function following ischemia in the diabetic rat heart. The beneficial effects of PLC are associated with enhanced mitochondrial oxidation of fuels.

Animals↗
PubMed2003

Deletion of mtDNA disrupts mitochondrial function and structure, but not biogenesis.

The role of nuclear DNA (nDNA)-encoded proteins in the regulation of mitochondrial fission and fusion has been documented, yet the role of mitochondrial DNA (mtDNA) and encoded proteins in mitochondrial biogenesis remains unknown. Long-term treatment of a lymphoblastoid cell line Molt-4 with ethidium bromide generated mtDNA-deficient rho0 mutants. Depletion of mtDNA in rho0 cells produced functional and morphological changes in mitochondria without affecting the nuclear genome and encoded proteins. Indeed, the gene encoding subunit II of mitochondrial cytochrome c oxidase (COX II), a prototypical mitochondrial gene, was reduced in rho0 mutants blunting the activity of mitochondrial cytochrome coxidase. Yet, the amount of the nuclear beta-actin gene and the activity of citrate synthase, a mitochondrial matrix enzyme encoded by nDNA, remained unaffected in rho0 cells. Loss of mtDNA in rho0 cells was associated with significant distortion of mitochondrial structure, decreased electron density of the matrix and disorganized inner and outer membranes, resulting in the appearance of 'ghost-like' mitochondria. However, the number of mitochondria-like structures was not significantly different between mtDNA-deficient and parental cells. Thus, we conclude that cells lacking mtDNA still generate mitochondrial scaffolds, albeit with aberrant function.

Journal Article↗
PubMed2002

Impairment of brain mitochondrial function by reactive nitrogen species: the role of glutathione in dictating susceptibility.

Mitochondrial enzymes involved in energy metabolism display varying degrees of sensitivity towards reactive nitrogen species such as peroxynitrite (ONOO-). With regards to the electron transport chain, cytochrome oxidase appears particularly sensitive. Inhibition of this component may lead to an increase in mitochondrial superoxide formation, exacerbation of cellular oxidative stress and further mitochondrial damage. Impairment of the electron transport chain may lead to a loss of membrane potential, ATP deficiency, opening of the permeability transition pore and the release of factors capable of initiating apoptosis. Reduced glutathione will react, via a number of diverse reactions, with reactive nitrogen species and hence is capable of limiting mitochondiral damage. Loss of brain glutathione may therefore be an important factor in those neurological conditions in which there is evidence of excessive nitric oxide formation and mitochondrial damage.

Animals↗