• Neonatal Medicine
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• v.17 no.2
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• pp.254-261
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• 2010

Little is known about neonatal mitochondrial disease, though mitochondrial metabolic disorders may often present in the neonatal period because of the high energy requirement of neonate. In newborn period, common presentations are not specific and the disease course may be rapid and fatal. In this study, we report three cases of neonatal mitochondrial disease. The first case was strongly suspected because of sudden seizure and mental change with severe lactic acidosis, and multiorgan failure. Plasma lactate/pyruvate (L/P) ratio was increased to 55.6 with marked lactic aciduria and increased plasma alanin up to 2,237 nmol/mL. In the second patient, a peritoneal dialysis was performed for acute adrenal and renal failure, but metabolic acidosis persisted. Plasma L/P ratio was increased to 23.9, and MRC I (mitochondrial respiratory chain defect) was diagnosed through the enzymatic analysis of the muscles. The third case showed repetitive episode of lactic acidosis during the first two months of life, hypotonia, failure to thrive and feeding difficulties. We found markedly increased cerebrospinal fluid L/P ratio up to 57 though plasma L/P ratio(19.4) was borderline with increased plasma lactate. The lactate peak was prominent in brain magnetic resonance spectroscopy (MRS). MRC II was confirmed through muscle biopsy. Plasma lactate level and lactate peak of brain MRS were normalized after conservative treatment.

• Journal of Life Science
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• v.22 no.12
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• pp.1621-1627
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• 2012

Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.473-491
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• 2007

Objectives : This study was designed to investigate the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines Methods : In this study, we measured the subsistence, form of NCI-H460 and A549 non-small-cell lung cancer cell by hemocytometer and DAPI staining. In each cell, we analyzed DNA fragmentation. reverse transcription-polymerase chain reaction and measured activity of caspase-3, caspase-8 and caspase-9. Results and Conclusions : We found that exposure of A549 cells to SGBPT resulted in growth inhibition in a dose-dependent manner. butSGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes. SGBPT treatment partially induced the expression of DR5 cells and the expression of Faswas markedly increased in both transcriptional and translational levels in A549 cells. SGBPT treatment partially induced the expression of Bcl-2, Bcl-XL and the expression of Bid was markedly decreased in translational levels in A549 cells. However, SGBPT treatment did not affect the expression of IAP family in A549 orNCI-H460 cells. SGBPT treatment partially induced the expression of caspase-3, caspase-8, caspase-9 activity which markedly increased in a dose-dependent manners in A549 cells. The fragmental development of PARP and ${\beta}$-catenin protein was observed in A549 cells by SGBPT treatment. SGBPT treatment induced the expression of PLC-${\gamma}1$ protein which decreased in A549 cells. SGBPT treatment partially induced the expression of DFF45/ICAD which markedly increased in a dose-dependent manner in A549 cells. Taken together. these findings suggested that SGBPT-induced inhibition of human lung carcinoma did not affect NCI-H460 cell growth. However, SGBPT-induced inhibition of human lung carcinoma A549 cell growth was associated with the induction of death receptor and mitochondrial pathway. The results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

• Molecules and Cells
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• v.23 no.3
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• pp.363-369
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• 2007

Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of $F_1/F_O$-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial $Ca^{2+}$ uniporter, and ruthenium red, an inhibitor of the mitochondrial $Ca^{2+}$ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the $F_1/F_O$-ATP synthase of mitochondria are important in regulating TRPM7 channels.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.258-267
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• 2006

Purpose : We have done this retrospective study to know the relative incidence and clinical manifestations of organic acidopathies in Korea during 8 years(from Jul. 1997 to May 2005). This results of organic acid analysis of 1,787 patients were compared with the results of organic acid analysis that were published three years ago. Methods : The results of quantitative organic acid analysis of samples of 1788 patients, referred from Jul. 1997 to May 2005, were analyzed retrospectively according to four age group(-2 mon, 3 mon-2 years, 3-12 years) and major clinical manifestations. Quantification of 83 organic acids was done with gas chromatography and mass spectometry. Results : We diagnosed 470 patients with 27 diseases of organic acid metabolism during this study period. Diseases found more than 10 cases are cytosolic 3-ketothiolase deficiency, mitochondrial respiratory chain disorders, PDHC deficiency, mitochondrial 3-ketothiolase deficiency, glutaric aciduria type II, biotinidase deficiency, methylmalonic aciduria and propionic aciduria. Other diseases were diagnosed in less than 10 cases. Conclusion : Though the incidence of individual organic acidemia is low, the overall incidence of organic acidemia as a whole seems to be relatively high in Korea. Compared with the results of organic acid analysis that were reported three years ago, we couldn't find a new disease and the difference of the relative incidences of high incident diseases. We were apprehensive of the errors that was owing to the short study period(3 years), but the relative incidences of our study(8 years) were similar to the results of organic acid analysis that were reported three years ago.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4745-4751
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• 2014

Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

• Journal of Ginseng Research
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• v.9 no.1
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• pp.86-94
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• 1985

Attempts were made if diol and triol fractions of ginseng saponin affect on glutamine transport into rat renal cortical mitochondria, swelling, phosphate dependent glutaminase activity, and consumption of oxygen. The following results were obtained. When mitochondrial preparation from rat renal cortex was incubated in medium containing 14C-glutamine and either triol or diol fractions, radioactivity was shown to increase at both 10-6% and 10-5% triol fractions of ginseng saponin, but reduce in case of diol fraction. The remarkable acceleration of the rate of swelling of renal cortical mitochondria was observed in the presence of 10-1% trios and diol fractions but no accerelation at lower concentrations. The activity of phosphate dependent glutaminase from renal cortical mitochondria was slightly activated at 10-2% of triol fraction. However, there was no effect in case of diol fraction. Oxygen consumption by mitochondria from renal cortex was remarkably increased at concentrations of 10-5% and 10-6% triol fractions, but reduced in the case of diol fractions. On the basis of these observations it was concluded that triol fraction of ginseng saponin might increase the transport of glutamine into mitochondria by accelerating the respiratory chain and supplying additional energy to mitochondria, and physiological role of triol fraction was entirely different from that of diol fraction of ginseng saponin.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.25-33
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• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Journal of Life Science
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• v.13 no.6
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• pp.933-942
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• 2003

CoenzymeQ is a quinone derivative with a long isoprenoid side chain. It transports electrons in the respiratory chain located in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes. It also functions as an antioxidant. Saccharomyces cerevisine coq mutants, that are deficient coenzyme Q biosynthesis fail to aerobically grow. They are not able to grow on non-fermentable carbon sources, such as glycerol, either The putative $coq^{-7}$ gene involved in coenzyme Q biosynthesis of Neurospora crassa was cloned and used for complementation of S. cerevisiae coq7 mutant. The predicted amino acid sequence of N. crassa COQ7 showed about 58% homology with Coq7p of S. cerevisiae. The growth rate of S. cerevisiae $coq^7$ mutant transformed with the N. crassa $coq^{-7}$ gene was restored to the wild-type level. The complemented 5. cerevisiae strain was able to grow with glycerol as a sole carbon source and showed less sensitivities to linolenic acid, a polyunsaturated fatty acid.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.163-166
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• 2010

Purpose : Leigh syndrome is a typical type of mitochondrial disease. This study was conducted to analyze the types of ophthalmologic symptoms and results of funduscopy conducted in the ophthalmologic examination of patients with Leigh syndrome. Methods : Funduscopy was conducted on 24 subjects, who were chosen among those diagnosed as having mitochondrial respiratory chain complex defect and who were clinically suitable for the criteria of Leigh syndrome. Their clinical features, ophthalmologic symptoms, and ophthalmologic examination results were retrospectively analyzed. Results : Of the 24 patients with Leigh syndrome, 11 developed ophthalmologic symptoms and no abnormal finding was observed in 13. The most frequent abnormal finding was visual disturbance in 5 patients. Funduscopy revealed abnormal findings in 17 patients; retinal pigmentation was the most frequent abnormality and was seen in 9 patients. Conclusion : Funduscopy can be an important screening test to find ophthalmologic abnormalities among patients with mitochondrial disease (MD), including those patients whose ophthalmologic symptoms are inconspicuous. It is predicted that an improved screening test can be made in the future that will identify risk factors related to ophthalmologic symptoms.