Epilepsy is arising from many molecular and biochemical events. In the underlying mechanisms of epilepsy, oxidative stress plays an important role in seizure-induced brain damage and neuronal death. Also epileptic seizures are noted in mitochondrial diseases with problems in oxidative phosphorylation. So oxidative stress is an important emerging cause of seizure-induced neuronal death as well as a result of epileptic seizure event.
Brain ; Epilepsy* ; Mitochondrial Diseases ; Neurons ; Oxidative Phosphorylation ; Oxidative Stress*

Oxidative Phosphorylation ; Acetylglucosamine ; Uridine Diphosphate N-Acetylglucosamine/metabolism*

Epilepsy is a neurological disorder from many molecular and biochemical responses. In the underlying mechanism, reactive oxygen species play an important role in seizure initiation and seizure-induced brain damage. In mitochondrial diseases, epileptic seizures are also noted from defects of oxidative phosphorylation. So oxidative stress from reactive oxygen species is important in mitochondrial dysfunction and epileptic seizure.
Brain ; Epilepsy* ; Mitochondria* ; Mitochondrial Diseases ; Nervous System Diseases ; Oxidative Phosphorylation ; Oxidative Stress ; Reactive Oxygen Species* ; Seizures

The ratio of acetoacetate to 8-hydroxybutyrate (ketone body ratio) in the blood may reflects the mitochondrial free NAD+/NADH ratio in the liver. Also arterial ketone body ratio will reflects the energy status of the hepatocytes, because mitochondrial free NAD+/NADH ratio is closely related to oxidative phosphorylation. Arterial ketone body ratio and osmolal gap, the difference between measured osmolality and calculated osmolality, were measured 30 min after the induction of hemorrhagic shock with mean arterial blood pressure at 40 mmHg in ten rabbits. Arterial ketone body ratios decreased significantly (p<0.05) from 0.74+/-0.17 to 0.38+/-0.09 and osmolal gap increased significantly (p<0.05) from 17.7+/-5.9 mOsm/Kg to 32.8+/-12.3 mOsm/Kg at 30 min after the induction of hemorrhagic shock. These results suggest that in hemorrhagic shock, decreased arterial ketone body ratio which reflects the inhibition of the TCA cycle is associated with increase of osmolal gap.
Arterial Pressure ; Hepatocytes ; Liver ; Osmolar Concentration ; Oxidative Phosphorylation ; Rabbits ; Shock, Hemorrhagic*

PURPOSE: The urinary bladder requires an adequate energy supply to maintain contractile function. The primary metabolic fuel is glucose. Through glycolysis and oxidative phosphorylation, high energy phosphate are generated, which in turn supply the metabolic energy for the contractile activities of the urinary bladder. The aim of this study was to determine the effects of glucose deprivation and recovery from glucose deprivation on the phasic and tonic components of the contractile responses of rabbit bladder strips to field stimulation, bethanechol, and KCl. MATERIALS AND METHODS: The urinary bladder bodies of mature male New Zealand White rabbits were separated from the base above the level of the ureteral orifices, and placed in Tyrode`s solution containing glucose in 37degrees C and equilibrated with 95% O2 and 5% CO2. Bethanechol(250microM) was left in contact with the strips for 4 minutes. KCI(120 mM) was left in contact with the strips for 4 minutes. Field stimulation(31Hz, 80V, 1ms) was maintained for 2 minutes. At the end of each incubation in glucose-free medium(100 minutes for FS, 180 minutes for KCl and bethanechol), the medium was changed to Tyrode`s solution containing glucose(1mg/ml) and stimulations continued for additional 90 minutes. Changes in muscle tension were measured and recorded on a Grass model 7D polygraph. RESULTS: The results can be summarized as follow : In response to glucose deprivation, (1) the tonic responses to field stimulation, bethanechol, and KCl all decreased at a significantly greater rate than the phasic responses; (2) the phasic and tonic responses to field stimulation were both reduced to less than 10% of control within 70 minutes of glucose deprivation; (3) the tonic response to bethanechol and KCl were reduced to approximately 10% of control within 180 minutes whereas the phasic responses remained stable at 40 and 30%, respectively; and (4) glucose replacement stimulated a rapid and nearly complete recovery of the phasic and tonic components of the response to field stimulation, bethanechol, and KCl. Concolusions: These results indicate that the tonic responses to all forms of stimulation are more sensitive to glucose deprivation than phasic responses.
Bethanechol ; Glucose* ; Glycolysis ; Humans ; Male ; Muscle Tonus ; Oxidative Phosphorylation ; Poaceae ; Rabbits ; Ureter ; Urinary Bladder*

Animals ; Brain ; cytology ; metabolism ; Denervation ; Mitochondria ; metabolism ; Oxidative Phosphorylation ; Rats ; Rats, Sprague-Dawley

Athletic performance is a complex multifactorial trait involving genetic and environmental factors. The heritability of an athlete status was reported to be about 70% in a twin study, and at least 155 genetic markers are known to be related with athlete status. Mitochondrial DNA (mtDNA) encodes essential proteins for oxidative phosphorylation, which is related to aerobic capacity. Thus, mtDNA is a candidate marker for determining physical performance. Recent studies have suggested that polymorphisms of mtDNA are associated with athlete status and/or physical performance in various populations. Therefore, we analyzed mtDNA haplogroups to assess their association with the physical performance of Korean population. The 20 mtDNA haplogroups were determined using the SNaPshot assay. Our result showed a significant association of the haplogroup F with athlete status (odds ratio, 3.04; 95% confidence interval, 1.094 to 8.464; p = 0.012). Athletes with haplogroup F (60.64 ± 3.04) also demonstrated a higher Sargent jump than athletes with other haplogroups (54.28 ± 1.23) (p = 0.041). Thus, our data imply that haplogroup F may play a crucial role in the physical performance of Korean athletes. Functional studies with larger sample sizes are necessary to further substantiate these findings.
Athletes ; Athletic Performance ; DNA, Mitochondrial ; Genetic Markers ; Humans ; Oxidative Phosphorylation ; Sample Size

In the present study, we have investigated the effect of metabolic inhibition on the inward rectifer K current (IK1). Using whole cell patch clamp technique we applied voltage ramp from +80 mV to -140 mV at a holding potential of -30 mV and recorded the whole cell current in single ventricular myocytes isolated from the rabbit heart. The current-voltage relationship showed N-shape (a large inward current and little outward current with a negative slope) which is a characteristic of IK1. Application of 0.2 mM dinitrophenol (DNP, an uncoupler of oxidative phosphorylation as a tool for chemical hypoxia) to the bathing solution with the pipette solution containing 5 mM ATP, produced a gradual increase of outward current followed by a gradual decrease of inward current with little change in the reversal potential (-80 mV). The increase of outward current was reversed by glibenclamide (10 muM), suggesting that it is caused by the activation of KATP. When DNP and glibenclamide were applied at the same time or glibenclamide was pretreated, DNP produced same degree of reduction in the magnitude of the inward current. These results show that metabolic inhibition induces not only the increase of KATP channel but also the decrease of IK1. Perfusing the cell with ATP-free pipette solution induced the changes very similar to those observed using DNP. Long exposure of DNP (30 min) or ATP-free pipette solution produced a marked decrease of both inward and outward current with a significant change in the reversal potential. Above results suggest that the decrease of IK1 may contribute to the depolarization of membrane potential during metabolic inhibition.
Adenosine Triphosphate ; Architectural Accessibility ; Baths ; Glyburide ; Heart ; Membrane Potentials ; Muscle Cells* ; Oxidative Phosphorylation

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

OBJECTIVE: To investigate the potential mechanisms that mediate the inhibitory effect of porcine recombinant NKlysin (prNK-lysin) against liver cancer cell metastasis. METHODS: HPLC-tandem mass spectrometry was used to identify the differentially expressed proteins in prNK-lysin-treated hepatocellular carcinoma SMMOL/LC-7721 cells in comparison with the control and PBS-treated cells. GO functional annotation and KEGG pathway analysis of the differentially expressed proteins were performed using GO and KEGG databases. RT-qPCR was used to determine the mRNA expression levels of polypeptide-N-acetylgalactosaminotransferase 13 (GALNT13), transmembrane protein 51 (TMEM51) and FKBP prolyl isomerase 3 (FKBP3) in the cells, and the protein expression of FKBP3 was verified using Western blotting. RESULTS: Proteomic analysis identified 1989 differentially expressed proteins in prNK-lysin-treated cells compared with the control cells, and 2753 compared with PBS-treated cells. Fifteen proteins were differentially expressed between PBS-treated and the control cells, and 1909 were differentially expressed in prNK- lysin group compared with both PBS and control groups. These differentially expressed proteins were involved mainly in the viral process, translational initiation and RNA binding and were enriched mainly in ribosome, protein process in endoplasmic reticulum, and RNA transport pathways. RT-qPCR showed that compared with the control group, prNK-lysin treatment significantly increased the mRNA expressions of GALNT13 (P < 0.05) and TMEM51 (P < 0.01) and lowered FKBP3 mRNA expression (P < 0.05). Western blotting also showed a significantly decreased expression of FKBP3 protein in prNK-lysin-treated cells (P < 0.001). CONCLUSION Treatment with prNK-lysin causes significant changes in protein expression profile of SMMOL/LC-7721 cells and inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 protein and affecting the cellular oxidative phosphorylation and glycolysis pathways.
Animals ; Swine ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Oxidative Phosphorylation ; Proteomics ; Glycolysis ; RNA, Messenger