Oxidative Phosphorylation in Hypoxic Airway Smooth Muscle

1974 ◽  
Vol 52 (1) ◽  
pp. 84-89 ◽  
Author(s):  
N. L. Stephens ◽  
J. Vogel
Keyword(s):  
Smooth Muscle ◽  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Energy Production ◽  
Respiratory Control ◽  
Mechanical Function ◽  
Loose Coupling ◽  
Experimental Conditions ◽  
Death Studies ◽  
Significant Difference

The impairment of mechanical function that we have previously reported in tracheal smooth muscle under conditions of hypoxia and substrate depletion may be due to a defect in the utilization of the energy produced, to a decrease in energy production in the muscle after the hypoxic inhibition of mitochondria, or to a combination of these. To test the second hypothesis mitochondria were isolated from the trachealis smooth muscle of dogs whose [Formula: see text] had been maintained at 30 mm Hg ± 7 (S.E.), for 1 h before death. Studies of oxidative phosphorylation revealed no significant differences in ADP/O ratios in these mitochondria as compared with normal nor was there any significant difference in rate of O2 uptake as long as ADP was available (state 3 respiration). However, there was a significant difference in respiratory control ratios (R.C.R.), generally regarded as the most sensitive biochemical index of the function integrity of mitochondria, as well as a significant difference between control and experimental conditions in the rate of O2 uptake when ADP was not available (state 4 respiration). These findings suggested loose coupling between electron transport and oxidative phosphorylation.

scholarly journals Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts

2004 ◽  
Vol 380 (3) ◽  
pp. 919-928 ◽  
Author(s):  
Eveline HUTTER ◽  
Kathrin RENNER ◽  
Gerald PFISTER ◽  
Petra STÖCKL ◽  
Pidder JANSEN-DÜRR ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Replicative Senescence ◽  
Citrate Synthase ◽  
Human Fibroblasts ◽  
Respiratory Control ◽  
Compensatory Mechanisms ◽  
Intact Cells ◽  
Atp Production ◽  
Human Diploid Fibroblasts

Limitation of lifespan in replicative senescence is related to oxidative stress, which is probably both the cause and consequence of impaired mitochondrial respiratory function. The respiration of senescent human diploid fibroblasts was analysed by highresolution respirometry. To rule out cell-cycle effects, proliferating and growth-arrested young fibroblasts were used as controls. Uncoupled respiration, as normalized to citrate synthase activity, remained unchanged, reflecting a constant capacity of the respiratory chain. Oligomycin-inhibited respiration, however, was significantly increased in mitochondria of senescent cells, indicating a lower coupling of electron transport with phosphorylation. In contrast, growth-arrested young fibroblasts exhibited a higher coupling state compared with proliferating controls. In intact cells, partial uncoupling may lead to either decreased oxidative ATP production or a compensatory increase in routine respiration. To distinguish between these alternatives, we subtracted oligomycin-inhibited respiration from routine respiration, which allowed us to determine the part of respiratory activity coupled with ATP production. Despite substantial differences in the respiratory control ratio, ranging from 4 to 11 in the different experimental groups, a fixed proportion of respiratory capacity was maintained for coupled oxidative phosphorylation in all the experimental groups. This finding indicates that the senescent cells fully compensate for increased proton leakage by enhanced electron-transport activity in the routine state. These results provide a new insight into age-associated defects in mitochondrial function and compensatory mechanisms in intact cells.

Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy

1970 ◽  
Vol 48 (9) ◽  
pp. 1037-1042 ◽  
Author(s):  
B. E. Jacobson ◽  
M. C. Blanchaer ◽  
K. Wrogemann
Keyword(s):  
Oxidative Phosphorylation ◽  
Tricarboxylic Acid Cycle ◽  
Respiratory Control ◽  
Test System ◽  
Loose Coupling ◽  
Dystrophic Muscle ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Uptake Rates ◽  
Late Stages

Skeletal muscle mitochondria were isolated from 33 dystrophic hamsters of the BIO 14.6 strain, aged 265 ± 13 (S.E.) days, by glass-on-glass homogenization in a sucrose–EDTA medium in the absence of the proteinase Nagarse. These organelles utilized O2 at half the normal rate with pyruvate/fumarate or palmitate as substrate in a manometric test system and exhibited decreased P/O ratios and phosphorylation rates with pyruvate/fumarate. In polarographic experiments the mitochondria from dystrophic muscle, supplemented with L-malate, had significantly depressed O2 uptake rates, respiratory control ratios, and phosphorylation rates with pyruvate, palmityl-L-carnitine, and acetyl-L-carnitine as substrates and low ADP/O ratios with pyruvate and palmityl-L-carnitine. Since the severity of the respiratory depression was similar with the three substrates, it appeared that the defect lay beyond acetyl-CoA in their common degradative pathway. Judging from the rapid rate of succinate and NADH oxidation, the respiratory chain was unimpaired. It was concluded that a defect was present in the tricarboxylic acid cycle of muscle mitochondria isolated without Nagarse from older dystrophic hamsters of the BIO 14.6 strain and that the defect was accompanied by a loose coupling of oxidative phosphorylation.

scholarly journals Studies on the Energy Metabolism of Human Leukocytes

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 168-175 ◽  
Author(s):  
JOHN M. FOSTER ◽  
MARY L. TERRY ◽  
Harriet Gunther
Keyword(s):  
Energy Metabolism ◽  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Respiratory Control ◽  
Endogenous Respiration ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Human Leukocytes ◽  
Endogenous Activity ◽  
Stimulation Of

Abstract 1. Oxidative phosphorylation has been studied in mitochondrial preparations from human leukocytes, using recently developed methods for homogenization, measuring respiration, and assaying for ATP. 2. Appreciable stimulation of both respiration and phosphorylation was limited to 3 substrates: succinate, malate, and α-glycerophosphate. The effects of other substrates were minimal. 3. The stimulating effects of these 3 substrates responded to inhibitors in a manner typical of mitochondrial oxidative phosphorylation. There was also considerable endogenous activity which, however, was insensitive to inhibitors. It is concluded the endogenous respiration and phosphorylation are not associated with electron transport. Subtracting their values from the data, P/O ratios consistent with good phosphorylation with the 3 substrates are obtained. 4. Studies with oligomycin and dinitrophenol suggest the presence of respiratory control. This indicates the mitochondria are intact. It is concluded that in the intact leukocyte the mitochondria are a major source of ATP.

Short-term variability in respiratory impedance and effect of deep breath in asthmatic and healthy subjects with airway smooth muscle activation and unloading

2013 ◽  
Vol 115 (5) ◽  
pp. 708-715 ◽  
Author(s):  
Alessandro Gobbi ◽  
Riccardo Pellegrino ◽  
Carlo Gulotta ◽  
Andrea Antonelli ◽  
Pasquale Pompilio ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Healthy Subjects ◽  
Muscle Activation ◽  
Respiratory Impedance ◽  
Short Term ◽  
Experimental Conditions ◽  
Significant Difference ◽  
Inspiratory Resistance ◽  
Short Term Variability

Inspiratory resistance (RINSP) and reactance (XINSP) were measured for 7 min at 5 Hz in 10 subjects with mild asymptomatic asthma and 9 healthy subjects to assess the effects of airway smooth muscle (ASM) activation by methacholine (MCh) and unloading by chest wall strapping (CWS) on the variability of lung function and the effects of deep inspiration (DI). Subjects were studied at control conditions, after MCh, with CWS, and after MCh with CWS. In all experimental conditions XINSP was significantly more negative in subjects with asthma than in healthy subjects, suggesting greater inhomogeneity in the former. However, the variability in both RINSP and XINSP was increased by either ASM activation or CWS, without significant difference between groups. DI significantly reversed MCh-induced changes in RINSP both in subjects with asthma and healthy subjects, but XINSP in the former only. This effect was impaired by CWS more in subjects with asthma than in healthy subjects. The velocity of RINSP and XINSP recovery after DI was faster in subjects with asthma than healthy subjects. In conclusion, these results support the opinion that the short-term variability in respiratory impedance is related to ASM tone or operating length, rather than to the disease. Nevertheless, ASM in individuals with asthma differs from that in healthy individuals in an increased velocity of shortening and a reduced sensitivity to mechanical stress when strain is reduced.

scholarly journals Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

2014 ◽  
Vol 307 (3) ◽  
pp. H346-H352 ◽  
Author(s):  
Song-Young Park ◽  
Jayson R. Gifford ◽  
Robert H. I. Andtbacka ◽  
Joel D. Trinity ◽  
John R. Hyngstrom ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Citrate Synthase ◽  
Smooth Muscles ◽  
Respiratory Control ◽  
Respiratory Control Ratio ◽  
Mitochondrial Content ◽  
Healthy Human

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s−1·mg−1, P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g−1·min−1, P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s−1·mg−1, P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

Relevance Predictability in Information Retrieval Systems

1967 ◽  
Vol 06 (02) ◽  
pp. 45-51 ◽  
Author(s):  
A. Kent ◽  
J. Belzer ◽  
M. Kuhfeerst ◽  
E. D. Dym ◽  
D. L. Shirey ◽  
...  
Keyword(s):  
Information Retrieval ◽  
Experimental Conditions ◽  
Treatment Groups ◽  
Retrieval Systems ◽  
Significant Difference ◽  
Information Retrieval Systems ◽  
High Predictability ◽  
Intermediate Response ◽  
Quantitative Indicators ◽  
Level Of Processing

An experiment is described which attempts to derive quantitative indicators regarding the potential relevance predictability of the intermediate stimuli used to represent documents in information retrieval systems. In effect, since the decision to peruse an entire document is often predicated upon the examination of one »level of processing« of the document (e.g., the citation and/or abstract), it became interesting to analyze the properties of what constitutes »relevance«. However, prior to such an analysis, an even more elementary step had to be made, namely, to determine what portions of a document should be examined.An evaluation of the ability of intermediate response products (IRPs), functioning as cues to the information content of full documents, to predict the relevance determination that would be subsequently made on these documents by motivated users of information retrieval systems, was made under controlled experimental conditions. The hypothesis that there might be other intermediate response products (selected extracts from the document, i.e., first paragraph, last paragraph, and the combination of first and last paragraph), that would be as representative of the full document as the traditional IRPs (citation and abstract) was tested systematically. The results showed that:1. there is no significant difference among the several IRP treatment groups on the number of cue evaluations of relevancy which match the subsequent user relevancy decision on the document;2. first and last paragraph combinations have consistently predicted relevancy to a higher degree than the other IRPs;3. abstracts were undistinguished as predictors; and4. the apparent high predictability rating for citations was not substantive.Some of these results are quite different than would be expected from previous work with unmotivated subjects.

Validation of a monetary Taylor Aggression Paradigm: Associations with trait aggression and role of provocation sequence

2020 ◽  
Author(s):  
J Konzok ◽  
L Kreuzpointner ◽  
GI Henze ◽  
L Wagels ◽  
C Kärgel ◽  
...  
Keyword(s):  
Random Sequence ◽  
Reactive Aggression ◽  
Reaction Time Task ◽  
Competitive Reaction ◽  
Experimental Conditions ◽  
Fixed Sequence ◽  
Taylor Aggression Paradigm ◽  
Trait Aggression ◽  
Significant Difference ◽  
In Series

© 2020 Elsevier Inc. The Taylor Aggression Paradigm (TAP) is widely used to measure reactive aggression in laboratory settings. While modified versions (mTAPs) with various stimulus characteristics (shocks, noise, pressure, heat) have already been established, a modified version with monetary stimuli has only been introduced very recently. In this experiment, 209 young healthy participants (104 males, 105 females) completed a mock Competitive Reaction Time Task (CRTT) with a fictional opponent with preprogrammed 40 win and 60 lose trials. In lose trials, participants were provoked by subtracting a low (0–20 euro cents), medium (30–60 cents) or high (70–90 cents) amount of money from their fictitious account. Provocation stimuli were either presented randomly or in a fixed sequence (experimental conditions). In contrast to a random sequence, the fixed sequence was generated by repeating trials from the same provocation category in series of three. Linear mixed models (LMMs) considering aggression trajectories revealed significant effects of provocation (low, medium, high) and trait aggression (K-FAF) on reactive aggression. Men showed significantly higher reactive aggression levels than women. In regard to provocation sequence, we found no significant difference in reactive aggression between the random vs. fixed stimulus sequences. The findings provide new evidence supporting the view that the monetary mTAP is able to induce as well as capture reactive aggression in the laboratory. Additionally, we found no advantage of a fixed sequence as the level of reactive aggression in a given trial appeared to be mainly predicted by the preceding provocation trial.

scholarly journals The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

2013 ◽  
Vol 305 (9) ◽  
pp. H1275-H1280 ◽  
Author(s):  
Yuh Fen Pung ◽  
Wai Johnn Sam ◽  
James P. Hardwick ◽  
Liya Yin ◽  
Vahagn Ohanyan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Synthesis ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Energy Production ◽  
Phenotypic Switching ◽  
Oxygen Species ◽  
Coronary Collateral ◽  
Collateral Growth

Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.

Dual Mutations Reveal Interactions Between Components of Oxidative Phosphorylation in Kluyveromyces lactis

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 929-938
Author(s):  
G D Clark-Walker ◽  
X J Chen
Keyword(s):  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Kluyveromyces Lactis ◽  
Mitochondrial Protein ◽  
Proton Pumping ◽  
Nuclear Genes ◽  
Suppressor Activity ◽  
Inner Membrane ◽  
Atp Production

Abstract Loss of mtDNA or mitochondrial protein synthesis cannot be tolerated by wild-type Kluyveromyces lactis. The mitochondrial function responsible for ρ0-lethality has been identified by disruption of nuclear genes encoding electron transport and F0-ATP synthase components of oxidative phosphorylation. Sporulation of diploid strains heterozygous for disruptions in genes for the two components of oxidative phosphorylation results in the formation of nonviable spores inferred to contain both disruptions. Lethality of spores is thought to result from absence of a transmembrane potential, ΔΨ, across the mitochondrial inner membrane due to lack of proton pumping by the electron transport chain or reversal of F1F0-ATP synthase. Synergistic lethality, caused by disruption of nuclear genes, or ρ0-lethality can be suppressed by the atp2.1 mutation in the β-subunit of F1-ATPase. Suppression is viewed as occurring by an increased hydrolysis of ATP by mutant F1, allowing sufficient electrogenic exchange by the translocase of ADP in the matrix for ATP in the cytosol to maintain ΔΨ. In addition, lethality of haploid strains with a disruption of AAC encoding the ADP/ATP translocase can be suppressed by atp2.1. In this case suppression is considered to occur by mutant F1 acting in the forward direction to partially uncouple ATP production, thereby stimulating respiration and relieving detrimental hyperpolarization of the inner membrane. Participation of the ADP/ATP translocase in suppression of ρ0-lethality is supported by the observation that disruption of AAC abolishes suppressor activity of atp2.1.

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