AN ENZYMATIC EVALUATION OF THIOL RADIOPROTECTORS

1966 ◽  
Vol 44 (3) ◽  
pp. 319-330 ◽  
Author(s):  
J. F. Scaife
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Respiration ◽  
Test System ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Level ◽  
Normal Tissues ◽  
Mixed Disulfide ◽  
Liver Homogenates ◽  
Protection Theory

A number of thiol and disulfide compounds have been tested for their ability to inhibit the oxidation of α-ketoglutarate by rat-liver homogenates. In general, a correlation exists between the degree of inhibition and the radioprotective ability of the compound. It is possible that a better correlation exists for the corresponding disulfides.The inhibition involves oxidation of the thiol, and the disulfides were found to be more potent inhibitors than the thiols.There is no change in the ATP level of normal tissues after the administration of aminoethylisothiouronium bromide hydrobromide in vivo, and the protective ability of this compound is not considered to be related to any interference with mitochondrial oxidative phosphorylation. Mitochondrial respiration is, however, inhibited. The results support the mixed disulfide protection theory of Eldjarn and Pihl, and provide a physiologically significant test system for this hypothesis.

Effects of cold stress on mitochondrial oxidative phosphorylation

1960 ◽  
Vol 199 (1) ◽  
pp. 201-202 ◽  
Author(s):  
Judith Patkin ◽  
E. J. Masoro
Keyword(s):  
Oxidative Phosphorylation ◽  
Cold Stress ◽  
Liver Mitochondria ◽  
The Other ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Tightly Coupled ◽  
Liver Homogenates ◽  
The One ◽  
Fasted Rats

The P:O ratio with succinate as substrate is the same for liver mitochondria from ‘cold-fasted’ rats as it is for mitochondria from control rats. Glucose-hexokinase acceptor studies with either succinate or glutamate as substrate indicate that the oxidative phosphorylating system is about as tightly coupled in the liver mitochondria from cold-fasted rats as it is in those from control rats. These results were surprising since earlier work with liver homogenates indicated that the efficiency of oxidative phosphorylation is markedly reduced in the homogenate from cold-fasted rats. The possible reasons for these differences in results with homogenates on the one hand and mitochondria on the other are discussed. The use of mitochondrial activities as an index of the efficiency of oxidative phosphorylation in vivo is also discussed.

scholarly journals Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
You Dong Liu ◽  
Xiao Peng Zhuang ◽  
Dong Lan Cai ◽  
Can Cao ◽  
Qi Sheng Gu ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Metabolic Reprogramming ◽  
Luciferase Reporter ◽  
Mitochondrial Oxidative Phosphorylation ◽  
In Vivo Assays ◽  
Reporter Assays ◽  
Extracellular Mirna

Abstract Background MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of miRNA in EV secretion from cancer cells remains unknown. Methods qPCR and bioinformatics analysis were applied for determining extracellular let-7a expression from CRC patient serum and cells. Nanosight particle tracking analysis was performed for investigating the effect of let-7a on EV secretion. Luciferase reporter assays was used for identifying targeted genes synaptosome-associated protein 23 (SNAP23). In vitro and in vivo assays were used for exploring the function of let-7a/SNAP23 axis in CRC progression. Bioenergetic assays were performed for investigating the role of let-7a/SNAP23 in cellular metabolic reprogramming. Results let-7a miRNA was elevated in serum EVs from CRC patients and was enriched in CRC cell-derived EVs. We determined that let-7a could suppress EV secretion directly targeting SNAP23. In turn, SNAP23 promotes EV secretion of let-7a to downregulate the intracellular let-7a expression. In addition, we found a novel mechanism of let-7a/SNAP23 axis by regulating mitochondrial oxidative phosphorylation (OXPHOS) through Lin28a/SDHA signaling pathway. Conclusions Let-7a plays an essential role in not only inhibiting EV secretion, but also suppressing OXPHOS through SNAP23, resulting in the suppression of CRC progression, suggesting that let-7a/SNAP23 axis could provide not only effective tumor biomarkers but also novel targets for tumor therapeutic strategies.

scholarly journals Skeletal muscle mitochondrial oxidative phosphorylation function in idiopathic pulmonary arterial hypertension: in vivo and in vitro study

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876829 ◽  
Author(s):  
Sasiharan Sithamparanathan ◽  
Mariana C. Rocha ◽  
Jehill D. Parikh ◽  
Karolina A. Rygiel ◽  
Gavin Falkous ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Oxidative Phosphorylation ◽  
Arterial Hypertension ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Pulmonary Vessels ◽  
Pulmonary Arterial

Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P-magnetic resonance spectroscopy (31P-MRS) and laboratory muscle biopsy analysis. 31P-MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.

scholarly journals Exosomal microRNA-503-3p derived from macrophages represses glycolysis and promotes mitochondrial oxidative phosphorylation in breast cancer cells by elevating DACT2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shulin Huang ◽  
Peizhi Fan ◽  
Chaojie Zhang ◽  
Jing Xie ◽  
Xiaowen Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Signaling Pathway ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Level ◽  
Glucose Intake ◽  
The Impact

AbstractMicroRNAs (miRNAs) are emerging drivers in tumor progression, while the role of miR-503-3p in breast cancer (BC) remains largely unknown. We aimed to explore the impact of macrophage-derived exosomal miR-503-3p in the development of BC by regulating disheveled-associated binding antagonist of beta-catenin 2 (DACT2). miR-503-3p and DACT2 expression in BC tissues and cells was assessed, and the expression of Wnt/β-catenin signaling pathway-related proteins in BC cells was also evaluated. Macrophages were induced and exosomes were extracted. The screened BC cell lines were, respectively, treated with exosomes, miR-503-3p inhibitor/mimic or upregulated/inhibited DACT2, and then the phenotypes, glucose intake, oxygen consumption rate, and adenosine-triphosphate (ATP) level of BC cells were determined. Cell growth in vivo was also observed. MiR-503-3p was elevated, DACT2 was reduced, and Wnt/β-catenin signaling pathway was activated in BC cells. Macrophage-derived exosomes, upregulated miR-503-3p or inhibited DACT2 promoted malignant behaviors of BC cells, glucose intake, and activity of the Wnt/β-catenin signaling pathway, while repressed oxygen consumption rate and ATP level in BC cells. Reversely, reduced miR-503-3p or upregulated DACT2 exerted opposite effects. This study revealed that reduction of macrophage-derived exosomal miR-503-3p repressed glycolysis and promoted mitochondrial oxidative phosphorylation in BC by elevating DACT2 and inactivating Wnt/β-catenin signaling pathway. Our research may provide novel targets for BC treatment.

scholarly journals Increased intramyocellular lipids but unaltered in vivo mitochondrial oxidative phosphorylation in skeletal muscle of adipose triglyceride lipase-deficient mice

2012 ◽  
Vol 303 (1) ◽  
pp. E71-E81 ◽  
Author(s):  
P. M. Nunes ◽  
T. van de Weijer ◽  
A. Veltien ◽  
H. Arnts ◽  
M. K. C. Hesselink ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Magnetic Resonance ◽  
Oxidative Phosphorylation ◽  
Muscle Performance ◽  
Resonance Spectroscopy ◽  
Lipolytic Enzyme ◽  
Adipose Triglyceride Lipase ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Triglyceride Lipase

Adipose triglyceride lipase (ATGL) is a lipolytic enzyme that is highly specific for triglyceride hydrolysis. The ATGL-knockout mouse (ATGL−/−) accumulates lipid droplets in various tissues, including skeletal muscle, and has poor maximal running velocity and endurance capacity. In this study, we tested whether abnormal lipid accumulation in skeletal muscle impairs mitochondrial oxidative phosphorylation, and hence, explains the poor muscle performance of ATGL−/− mice. In vivo 1H magnetic resonance spectroscopy of the tibialis anterior of ATGL−/− mice revealed that its intramyocellular lipid pool is approximately sixfold higher than in WT controls ( P = 0.0007). In skeletal muscle of ATGL−/− mice, glycogen content was decreased by 30% ( P < 0.05). In vivo 31P magnetic resonance spectra of resting muscles showed that WT and ATGL−/− mice have a similar energy status: [PCr], [Pi], PCr/ATP ratio, PCr/Pi ratio, and intracellular pH. Electrostimulated muscles from WT and ATGL−/− mice showed the same PCr depletion and pH reduction. Moreover, the monoexponential fitting of the PCr recovery curve yielded similar PCr recovery times (τPCr; 54.1 ± 6.1 s for the ATGL−/− and 58.1 ± 5.8 s for the WT), which means that overall muscular mitochondrial oxidative capacity was comparable between the genotypes. Despite similar in vivo mitochondrial oxidative capacities, the electrostimulated muscles from ATGL−/− mice displayed significantly lower force production and increased muscle relaxation time than the WT. These findings suggest that mechanisms other than mitochondrial dysfunction cause the impaired muscle performance of ATGL−/− mice.

scholarly journals TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma

2019 ◽  
Author(s):  
Yi Fu ◽  
Dongdong Wang ◽  
Huaishan Wang ◽  
Menghua Cai ◽  
Chao Li ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Translocator Protein ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Diagnostic Biomarkers ◽  
Extracellular Flux ◽  
Glioma Cell Proliferation ◽  
Glioma Growth ◽  
Proliferation In Vitro

Abstract Background The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions of TSPO in vivo and its role in glioma tumorigenesis remain elusive. Methods TSPO knockout xenograft and spontaneous mouse glioma models were employed to assess the roles of TSPO in the pathogenesis of glioma. A Seahorse Extracellular Flux Analyzer was used to evaluate mitochondrial oxidative phosphorylation and glycolysis in TSPO knockout and wild-type glioma cells. Results TSPO deficiency promoted glioma cell proliferation in vitro in mouse GL261 cells and patient-derived stem cell–like GBM1B cells. TSPO knockout increased glioma growth and angiogenesis in intracranial xenografts and a mouse spontaneous glioma model. Loss of TSPO resulted in a greater number of fragmented mitochondria, increased glucose uptake and lactic acid conversion, decreased oxidative phosphorylation, and increased glycolysis. Conclusion TSPO serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis. 1. TSPO deficiency promotes glioma growth and angiogenesis. 2. TSPO regulates the balance between mitochondrial oxidative phosphorylation and glycolysis.

scholarly journals Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Bo Li ◽  
Yin Yu ◽  
Yanan Jiang ◽  
Lili Zhao ◽  
Ang Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Oxidative Phosphorylation ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Major Type ◽  
High Morbidity ◽  
Mitochondrial Oxidative Phosphorylation

AbstractEsophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation.

Alterations of mitochondria in liver but not in heart homogenates after treatment of rats with benznidazole

2014 ◽  
Vol 33 (10) ◽  
pp. 1066-1070 ◽  
Author(s):  
DA Rendon
Keyword(s):  
Oxidative Phosphorylation ◽  
Day Treatment ◽  
Respiratory Control ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Inner Mitochondrial Membrane ◽  
Oral Gavage ◽  
Daily Dose ◽  
Female Wistar Rats ◽  
Proton Leakage ◽  
Liver Homogenates

The mitochondrial oxidative phosphorylation system was studied in liver and heart homogenates after treatment of rats with benznidazole. The drug was given by oral gavage to adult female Wistar rats for 9 consecutive days (100 mg benznidazole/kg body weight as a daily dose). The mitochondrial state 4 and state 3 respiration rates, respiratory control, efficiency of oxidative phosphorylation (ADP/O), and ATPsynthase activity were assayed. The results showed that according to all these parameters, the mitochondria in cardiac homogenates were not affected in the rats treated with benznidazole. By contrast, mitochondria in the liver homogenates of drug-treated rats were altered, showing decreased respiratory control and a lower coefficient of ADP/O as a result of an increase in the state 4 respiration rate. These data indicate the possibility of production of an uncoupling factor leading to increased proton leakage through the inner mitochondrial membrane as a result of a 9-day treatment of rats with benzonidazole. The obtained experimental data might at least partly explain the nature of benznidazole toxicity in the liver treated with benznidazole.

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