• Plant Biotechnology Reports
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• 제4권4호
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• pp.281-291
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• 2010

The rice CHLH gene encodes the $Mg^{2+}$-chelatase H subunit, which is involved in chlorophyll biosynthesis. Growth of the chlorophyll-deficient oschlh mutant is supported by mitochondrial activity. In this study, we investigated the activity of mitochondrial respiration in the illuminated leaves during oschlh seedling development. Growth of mutant plants was enhanced in the presence of 3% sucrose, which may be used by mitochondria to meet cellular energy requirements. ATP content in these mutants was, however, significantly lowered in light conditions. Low cytosolic levels of NADH in illuminated oschlh mutant leaves further indicated the inhibition of mitochondrial metabolism. This down-regulation was particularly evident for oxidative stressresponsive genes in the mutant under light conditions. Hydrogen peroxide levels were higher in oschlh mutant leaves than in wild-type leaves; this increase was largely caused by the impairment of the expression of the antioxidant genes, such as OsAPXl, OsRACl, and OsAOXc in knockout plants. Moreover, treatment of mesophyll protoplasts with ascorbic acid or catalase recovered ATP content in the mutants. Taken together, these results suggest that the light-mediated inhibition of mitochondrial activity leads to stunted growth of CHLH rice seedlings.

• Journal of Ginseng Research
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• 제43권4호
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• pp.517-526
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• 2019

Background: The root of Panax ginseng, a member of Araliaceae family, has been used as herbal medicine and functional food in Asia for thousands of years. According to Traditional Chinese medicine, ginseng is the most widely used "Qi-invigorating" herbs, which provides tonic and preventive effects by resisting oxidative stress, influencing energy metabolism, and improving mitochondrial function. Very few reports have systematically measured cell mitochondrial bioenergetics after ginseng treatment. Methods: Here, H9C2 cell line, a rat cardiomyoblast, was treated with ginseng extracts having extracted using solvents of different polarity, i.e., water, 50% ethanol, and 90% ethanol, and subsequently, the oxygen consumption rate in healthy and tert-butyl hydroperoxideetreated live cultures was determined by Seahorse extracellular flux analyzer. Results: The 90% ethanol extracts of ginseng possessed the strongest antioxidative and tonic activities to mitochondrial respiration and therefore provided the best protective effects to H9C2 cardiomyocytes. By increasing the spare respiratory capacity of stressed H9C2 cells up to three-folds of that of healthy cells, the 90% ethanol extracts of ginseng greatly improved the tolerance of myocardial cells to oxidative damage. Conclusion: These results demonstrated that the low polarity extracts of ginseng could be the best extract, as compared with others, in regulating the oxygen consumption rate of cultured cardiomyocytes during mitochondrial respiration.

• BMB Reports
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• 제37권4호
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• pp.454-459
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• 2004

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% $O_2$, 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.

• Journal of Ginseng Research
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• 제47권2호
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• BMB Reports
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• 제51권11호
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• pp.590-595
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• 2018

Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4-phenylpyridinium $(MPP^+)$-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against $MPP^+$-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated $MPP^+$-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of $MPP^+$-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, $Ca^{2+}$, and ATP in $MPP^+$-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against $MPP^+$-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.225-241
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• 2018

Taurine is an abundant, ${\beta}-amino$ acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.

• Animal cells and systems
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• 제16권1호
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• BMB Reports
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• 제52권4호
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• pp.250-258
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• 2019

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective and progressive loss of dopaminergic neurons. Genetic and environmental risk factors are associated with this disease. The genetic factors are composed of approximately 20 genes, such as SNCA, parkin, PTEN-induced kinase1 (pink1), leucine-rich repeat kinase 2 (LRRK2), ATP13A2, MAPT, VPS35, and DJ-1, whereas the environmental factors consist of oxidative stress-induced toxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), rotenone, and paraquat. The analyses of their functions and mechanisms have provided important insights into the disease process, which has demonstrated that these factors cause oxidative damage and mitochondrial dysfunction. The most invaluable studies have been performed using disease model organisms, such as mice, fruit flies, and worms. Among them, Drosophila melanogaster has emerged as an excellent model organism to study both environmental and genetic factors and provide insights to the pathways relevant for PD pathogenesis, facilitating development of therapeutic strategies. In this review, we have focused on the fly model organism to summarize recent progress, including pathogenesis, neuroprotective compounds, and newer approaches.

• 생약학회지
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• 제52권3호
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• pp.149-156
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• 2021

Excessive glutamate can cause oxidative stress in neuronal cells and this can be the reason for neurodegenerative disease. In this study, we investigated the protective effect of Spirulina maxima hot ethanol extract on mouse hippocampal HT22 cell of which glutamate receptor has no function. HT22 cells were pre-treated with S. maxima sample at a dose dependent manner (1, 10 and 100 ㎍/ml). After an hour, glutamate was treated. Cell viability, reactive oxygen species (ROS) accumulation, Ca²⁺ influx, decrease of mitochondrial membrane potential level and glutathione related assays were followed by then. S. maxima ethanol extract improved the cell viability by suppressing the ROS and Ca²⁺ formation, retaining the mitochondrial membrane potential level and protecting the activity of the antioxidant enzymes compared with group of vehicle-treated controls. These suggest that S. maxima may decelerate the neurodegeneration by attenuating neuronal damage and oxidative stress.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.85-91
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• 2019

Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.