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 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to evaluate the relationship between physical performance capacity and the mitochondrial content of skeletal muscle. Four groups of rats were trained by means of treadmill running 5 days/wk for 13 wk. One group ran 10 min/day, a second group ran 30 min/day, a third group ran 60 min/day, and a fourth group ran 120 min/day. The magnitude of the exercise-induced adaptive increase in gastrocnemius muscle respiratory capacity varied over a twofold range in the four groups. There were significant correlations between the levels of three mitochondrial markers (cytochrome c, citrate synthase, respiratory capacity) in the animals' gastrocnemius muscles and the duration of a run to exhaustion. There was also a significant correlation between the amounts of glycogen remaining in liver and skeletal muscle after a 30-min-long exercise test and the respiratory capacity of the animal's leg muscles. These findings are compatible with the interpretation that a close relationshiop exists between skeletal muscle mitochondrial content and the capacity to perform endurance exercise.
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PMID:Skeletal muscle respiratory capacity, endurance, and glycogen utilization. 1816 Apr 57

Cytochrome aco purified from an alkalophilic bacterium grown at pH 10 contains hemes a, b, and c as prosthetic groups, and their redox behavior was examined by using stopped-flow and rapid-scan techniques. Under anaerobic conditions the reduction of both heme a and c moieties with dithionite proceeded exponentially but with different rates, usually the former being reduced about 4 times faster than the latter. The reduction of protoheme was much slower, and a time-difference spectrum for this species was of a high spin type with absorption peaks at 433, 557, and 609 nm. Only the protoheme combined with CO, fulfilling the criteria for cytochrome o. Potentiometric titrations determined a midpoint potential of c heme to be 95 mV at pH 7.0 and 25 degrees C and suggested the presence of two forms of a heme with midpoint potentials of 250 and 323 mV. Cytochrome aco utilizes ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) to reduce oxygen relatively rapidly without added cytochrome c (Qureshi, M. H., Yumoto, I., Fujiwara, T., Fukumori, Y., Yamanaka, T. (1990) J. Biochem. 107, 480-485). During the steady state, however, heme a stayed almost fully reduced in contrast to a partial reduction of heme c. Even after exhaustion of the dissolved oxygen the extent of reduction of heme c was 60-70% that attained by the dithionite reduction. When ascorbate plus TMPD-reduced cytochrome aco was exposed to oxygen the reduced heme c was oxidized rapidly whereas the oxidation of reduced a heme was negligibly slow. The full reduction of heme a during the steady state and its extremely slow oxidation rendered participation of heme a in the oxidase reaction less likely. A novel peak appearing transiently around 567 nm during the reaction was tentatively ascribed to an intermediate form of protoheme, or o heme, which was thus supposed to react directly with molecular oxygen. These results suggest strongly that the main electron transfer pathway would be c----o----oxygen. A possible role of a in regulating the electron flow through the main pathway and its functional relationship to a heme in the aa3-type cytochrome oxidase were discussed.
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PMID:Stopped-flow and rapid-scan studies of the redox behavior of cytochrome aco from facultative alkalophilic Bacillus. 186 Aug 40

The two unlinked genes CYC1 and CYC7 encode iso-1-cytochrome c and iso-2-cytochrome c, respectively, in the yeast Saccharomyces cerevisiae. An examination of the steady-state level of CYC1 and CYC7 mRNAs in normal and mutant strains grown under different conditions, along with previous results of apoprotein levels, demonstrate that CYC1 and CYC7 have similar and different modes of regulation. Both CYC1 and CYC7 mRNAs are diminished after anaerobic growth. In contrast, CYC1 mRNA but not CYC7 mRNA is decreased by heme deficiency in hem1 mutants. Although both CYC1 and CYC7 mRNAs are substantially lowered after growth in glucose medium, there is a difference in the kinetics of glucose derepression. CYC1 mRNA levels rise in the early logarithmic phase of growth before complete exhaustion of glucose, whereas CYC7 mRNA levels rise in the late logarithmic phase when the level of CYC1 mRNA has plateaued. For a brief period before cessation of growth, the level of CYC7 mRNA attains a level corresponding to the high derepressed level of CYC1 mRNA. The high amount of CYC7 mRNA is surprising because iso-2-cytochrome c constitutes only 5% of the total cytochrome c complement in derepressed cells. We suggest that iso-2-cytochrome c has the potential to comprise a major proportion of cytochrome c under certain physiologic conditions that have not been experimentally defined. The cyc3 mutant, which lacks the ability to attach heme groups to apocytochromes c, contains both CYC1 and CYC7 mRNAs in normal amounts. Yet, cyc3 mutants contain only apoiso-2-cytochrome c and not apoiso-1-cytochrome c. The lack of accumulation of apoiso-1-cytochrome c in cyc3 mutants, which contain CYC1 mRNA, suggests that apoiso-1-cytochrome c is extensively regulated by a post-transcriptional process.
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PMID:Differential regulation of the duplicated isocytochrome c genes in yeast. 608 25

Addition of exogenous NADH to rotenone- and antimycin A-treated mitochondria, in 125 mM KCl, results in rates of oxygen uptake of 0.5-1 and 10-12 nanoatoms of oxygen X mg protein-1 X min-1 in the absence and presence of cytochrome c, respectively. During oxidation of exogenous NADH there is a fast and complete reduction of cytochrome b5 while endogenous or added exogenous cytochrome c become 10-15% and 100% reduced, respectively. The reoxidation of cytochrome b5, after exhaustion of NADH, precedes that of cytochrome c. NADH oxidation is blocked by mersalyl, an inhibitor of NADH-cytochrome b5 reductase. These observations support the view of an electron transfer from the outer to the inner membrane of intact mitochondria. Both the rate of exogenous NADH oxidation and the steady state level of cytochrome c reduction increase with the increase of ionic strength, while the rate of succinate oxidation undergoes a parallel depression. These observations suggest that the functions of cytochrome c as an electron carrier in the inner membrane and as an electron shuttle in the intermembrane space are alternative. It is concluded that aerobic oxidation of exogenous NADH involves the following pathway: NADH leads to NADH-cytochrome b5 reductase leads to cytochrome b5 leads to intermembrane cytochrome c leads to cytochrome oxidase leads to oxygen. It is suggested that the communication between the outer and inner membranes mediated by cytochrome c may affect the oxidation-reduction level of cytosolic NADH and the related oxidation-reduction reactions.
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PMID:Cytochrome c as an electron shuttle between the outer and inner mitochondrial membranes. 626 41

This study was undertaken to evaluate the effects of various training frequencies on performance capacity, the mitochondrial marker cytochrome c, and myoglobin, which is responsible for storage and transport of O2, in the three types of skeletal muscle. Female rats were trained by treadmill running up to 120 min/day, either 2, 4, or 6 days/wk for 14 wk. As a result of training, exercise time to exhaustion was increased in proportion to the number of training sessions per week. Cytochrome c concentration increased (range 20-90%) as a linear function of the number of exercises per week in the fast-twitch red vastus lateralis (FTR), the slow-twitch soleus (STR), and the mixed plantaris muscles. However, the concentration of cytochrome c in fast-twitch white vastus lateralis (FTW) muscles increased to approximately the same extent (40-50%) in all training groups. The increases in myoglobin concentration (13-45%) with training were significantly related to frequency in FTR muscle but not in STR muscle. Myoglobin levels in FTW muscle remained unchanged, regardless of training group. These results provide evidence that the capacity to perform endurance exercise and the mitochondrial content of the red skeletal muscle types are directly affected by training frequency.
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PMID:Skeletal muscle cytochrome c and myoglobin, endurance, and frequency of training. 627 38

It has been shown that in bovine heart submitochondrial particles, antimycin and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) inhibit the oxidation of NADH, succinate, and reduced ubiquinone incompletely, the uninhibited rate being about 20-40 nmol of substrate oxidized min-1 (mg of protein)-1. By contrast, rotenone, cyanide, BAL (2,3-dimercaptopropanol), and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole [Trumpower, B. L., & Haggerty, J. G. (1980) J. Bioenerg. Biomembr. 12, 151-164] caused essentially complete inhibition when added alone or after maximal inhibition by antimycin or HQNO. Having thus ascertained that the electron leak through the antimycin block appeared to follow the normal path through complex III (ubiquinol: cytochrome c oxidoreductase) and cytochrome oxidase, the reduction of the b cytochromes by substrates and their oxidation through the leak in the antimycin block by molecular oxygen were studied. It was shown that at normal electron flux from NADH and succinate, both cytochromes b562 and b566 were reduced in antimycin-treated submitochondrial particles. Their oxidation after substrate exhaustion was biphasic, however. At 565 minus 575 nm, 56% of the total reduced cytochrome b was oxidized through the leak in the antimycin block at a more rapid rate, while the remaining 44% was oxidized about 10 times slower. When electron flux from substrates to complex III was slowed down by the use of inhibitors or substrates at less than or equal to 0.1 Km concentration, then only reduced b562 accumulated in antimycin-treated particles. The oxidation of b562 after substrate exhaustion or inhibition of substrate oxidation by an appropriate inhibitor occurred at a rate comparable to that of the slower reoxidation phase described above. These results indicated, therefore, that cytochromes b566 and b562 are oxidized through the leak in the antimycin block at two different rates, the reoxidation rate of b566 being about 10 times faster than that of b562. The implications of these findings on the kinetic relationship of these two cytochromes in the respiratory chain have been discussed.
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PMID:Kinetics of cytochrome b oxidation in antimycin-treated submitochondrial particles. 715 May 80

Oxygen release accompanying oxidation of vanadyl by diperoxovanadate was suppressed on addition of NADH. The added NADH was rapidly oxidized, oxygen in the medium was consumed, and the reaction terminated on exhaustion of either NADH or vanadyl. The consumption of oxygen and disappearance of NADH needed small concentrations of diperoxovanadate to initiate and increased with increase in the concentration of vanadyl and NADH or decrease of pH. The products of the reaction were found to be NAD+ from NADH and vanadate oligomers from vanadyl and oxygen. The reaction was insensitive to catalase and was not dependent on H2O2. The reaction was inhibited by superoxide dismutase, cytochrome c, EDTA, Mn2+, histidine, and DMPO, but not by hydroxyl radical scavengers such as ethanol and benzoate. The ESR spectrum of the reaction mixture showed the presence of the 1:2:2:1 quartet signal typical of a DMPO-OH adduct, but this was not modified by ethanol. This oxygen radical species, possibly of .OV type derived from diperoxovanadate, is proposed to have a role in the reactions of oxygen release and NADH oxidation.
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PMID:Requirement of a diperoxovanadate-derived intermediate for the interdependent oxidation of vanadyl and NADH. 784 Jun 32

Myocytes prepared from perfused rat heart were studied spectroscopically using a photodiode array spectrophotometer adapted to a rapid mixing stopped-flow apparatus. The isolated cells were found to be viable for 3 to 4 hours, i.e. over the total time of the experiments. Sodium ascorbate and tetramethyl-para-phenylenediamine were used as exogenous reductants. Cytoplasmic and mitochondrial membranes were found to be freely permeable to tetramethyl-para-phenylenediamine. The use of singular value decomposition proved to be powerful in resolving the spectral contributions of the chromophoric components within the overall absorption spectrum. Spectral resolution was improved by adding carbon monoxide at a concentration that kept myoglobin fully saturated without affecting the activity of cytochrome c oxidase. The redox state of cytochrome c and cytochrome a was observed during the steady-state consumption of oxygen and during the reduction following the exhaustion of oxygen. The redox state of the two chromophores was found to be approximately equal and close to 25-30% oxidized during steady-state respiration; during the final reduction they changed simultaneously. These experiments suggest that in living cells, as in the purified enzyme, the rate limiting step of the turnover of cytochrome oxidase is the internal transfer of electrons from cytochrome a to cytochrome a3.
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PMID:Time-resolved optical spectroscopy on intact myocytes. 838 21

The study was designed to investigate the role of hyperthermia in the tolerance of exercise in rats and the possible mechanism was examined. The hyperthermic pretreatment was performed using an electric pad on the anesthesized rats 24 hours before exercise. Rats were exercised passively in a motor-controlled round treadmill in high temperature environment (36-37 degrees C) until exhaustion. The capacity of tolerance was calculated. Lymphocytes and gastrocnemius muscle were collected from both groups. The changes in muscular morphology, mitochondria oxidative enzyme activity and induction of Hsp72 were investigated. The results revealed that experimental rats were more tolerant to exercise at high temperature than the control group; the duration time were 89 +/- 17.8 min and 63.1 +/- 7.3 min, respectively. Hsp72 was induced markedly in the experimental group, both in muscle and lymphocytes, indicating a heat shock response. There was no significant change in morphology of the mitochondria, 24 hours after hyperthermic treatment, as shown by histopathological and electromicroscopic investigation. However, the activity of mitochondrial enzymes increased significantly in experimental group before exercise: 84.6 +/- 6.3 and 345 +/- 15.4 (nmole cytochrome c/min/mg total protein) respectively of NADH-cytochome c reductase and succinate-cytochome c reductase activity in experimental group compared to 58.9 +/- 4.7 and 269.0 +/- 24.0 in control group (p < 0.05, by student t-test). It is concluded that hyperthermic treatment enhances muscular mitochondrial oxidative enzyme activity in rats, and results in increasing tolerance to exercise at high temperature. The heat shock response, most probably the inducible Hsp72, is a crucial factor in this effect.
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PMID:Previous hyperthermic treatment increases mitochondria oxidative enzyme activity and exercise capacity in rats. 1060 4

Apoptosis and necrosis are distinct forms of cell death that occur in response to various agents. We studied the action of N-Acetyl-D-sphingosine (C2-ceramide) or N-hexanoyl-D-sphingosine (C6-ceramide) in human hepatoma HepG2 cell line. The cells were treated in vitro for 1-24 h. Cell toxicity was evaluated by MTT assay. DNA content was estimated by gel electrophoresis and flow cytometry. Measurement of mitochondrial respiration, analysis of cytochrome c release and caspase-3 activation were assessed in order to determine if either of these events in the induction of apoptosis and/or necrosis was predominant. We have demonstrated that C2 and C6-ceramide were cytotoxic in a time and dose-dependent manner. After 24 h of treatment with 100 microM of C2 and C6 the morphology (May-Giemsa staining) of treated cells displayed an apoptotic phenotype in C6-treated cells, confirmed by a high (sub-G1 peak > 20%) proportion by flow cytometry while a necrotic morphology was observed after C2-ceramide treatment, confirmed by DNA smearing in DNA electrophoresis. After C6-ceramide incubation, the respiratory chain was functional only slightly inhibited (20%), there was production of ATP, cytochrome c release without ROS production, activation of caspase-3 and induction of apoptosis. On the contrary, C2-ceramide inhibited the respiratory chain more intensely (80%) increased significantly ROS production, which resulted in an arrest of ATP production, no cytochrome c release and absence of caspase-3 activation. Finally after complete exhaustion of intracellular ATP, mitochondrial explosion induced necrotic cell death. In conclusion, evidence suggest that mitochondrial respiratory chain function is essential for controlling the decision of the cell to enter a apoptotic or necrosis process.
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PMID:Commitment to apoptosis by ceramides depends on mitochondrial respiratory function, cytochrome c release and caspase-3 activation in Hep-G2 cells. 1467 99


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