• 제목/요약/키워드: Mitochondrial medicine

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Silibinin Induces Apoptotic Cell Death Via ROS-dependent Mitochondrial Pathway in Human Glioma Cells

  • Shin, Won-Yong;Jeong, Ji-Cheon
    • 동의생리병리학회지
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    • 제23권4호
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    • pp.888-894
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    • 2009
  • It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

Mori Fructus Induces Cell Death through ROS-dependent Mitochondrial Apoptotic Pathway in Human Glioma Cells

  • Jang, Sang-Won;Jeong, Ji-Cheon
    • 동의생리병리학회지
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    • 제22권5호
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    • pp.1322-1329
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    • 2008
  • Mulberry has been reported to contain wide range of polyphenols and have chemopreventive activity. However, little has been known regarding the effect of mulberry fruits on cell viability in human glioma cells. The present study was undertaken to examine the effect of mulberry fruit (Mar; Fructus) on cell viability and to determine its underlying mechanism in human glioma cells. Cell viability and cell death were estimated by MTT assay and trypanblue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. The mitochondrial transmembrane potential was measured with $DiOC_6$(3). Bax expression and cytochrome c release were measured by Western blot analysis. Caspase activity was estimated using colorimetric kit. Mori Fructus resulted in apoptotic cell death in a dose- and time-dependent manner. Mori Fructus increased ROS generation and the Mori Fructus-induced cell death was also prevented by antioxidants, suggesting that ROS generation plays a critical role in Mari Fructus-induced cell death. Western blot analysis showed that Mori Fructus treatment caused an increase in Bax expression, which was inhibited by the antioxidant N-acetylcysteine (NAC). Mori Fructus induced depolarization of mitochondrial membrane potential and its effect was inhibited by the antioxidants NAC and catalase. Mori Fructus induced cytochrome c release, which was inhibited by NAC. Caspase activity was stimulated by Mori Fructus and caspase inhibitors prevented the Mori Fructus-induced cell death. These findings suggest that Mori Fructus results in human glioma cell death through ROS-dependent mitochondrial pathway in human glioma cells.

심경, 신경의 오수혈 침자가 Mitochondrial Respiratory Chain Complexes에 미치는 영향 (The Effects of Acupuncture at Heart and Kidney Meridian on Mitochondrial Respiratory Chain Complexes Activities in Rats)

  • 최동희;이유미;김미래;박정혜;김혜란;나창수;윤대환
    • Korean Journal of Acupuncture
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    • 제37권1호
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    • pp.37-45
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    • 2020
  • Objectives : Mitochondria are typically known as intracellular double membrane-bound structures that supply energy for intracellular metabolism including Krebs cycle and beta-oxidation. Also, acupuncture has been known to stimulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activities in rat's heart and kidneys, the activities of mitochondrial respiratory chain complexes I to IV were observed. Methods : The rats were divided into 11 groups; Normal (no acupuncture treatment and under anesthesia for 10 min), heart meridian five-transport-points (acupuncture treatment at HT9, HT8, HT7, HT4 and HT3 under anesthesia for 10 min), and kidney meridian five-transport-points (acupuncture treatment at KI1, KI2, KI3, KI7 and KI10 under anesthesia for 10 min). All rats were sacrificed and the heart and kidneys were examined for the changes of respiratory chain activities. Results : Acupuncture at HT7 increased the activity of succinate dehydrogenase; acupuncture at KI2 increased the activity of ubiquinol cytochrome C oxidoreductase; and acupuncture at HT9, HT8, HT3 and KI1 increased activities of cytochrome C oxidase. Conclusions : Acupuncture assists mitochondrial repiratory chain activity via the Cytochrome C oxidase signaling pathway in heart and kidney of rats.

Mitochondrial DNA Sequence Variability of Spirometra Species in Asian Countries

  • Jeon, Hyeong-Kyu;Eom, Keeseon S.
    • Parasites, Hosts and Diseases
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    • 제57권5호
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    • pp.481-487
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    • 2019
  • Mitochondrial DNA sequence variability of Spirometra erinaceieuropaei in GenBank was observed by reinvestigation of mitochondrial cox1 and cytb sequences. The DNA sequences were analyzed in this study, comprising complete DNA sequences of cox1 (n=239) and cytb (n=213) genes. The 10 complete mitochondrial DNA sequences of Spirometra species were compared with those of Korea, China and Japan. The sequences were analyzed for nucleotide composition, conserved sites, variable sites, singleton sites and parsimony-informative sites. Phylogenetic analyses was done using neighbor joining, maximum parsimony, Bayesian inference and maximum-likelihood on cox1 and cytb sequences of Spirometra species. These polymorphic sites identified 148 (cox1) and 83 (cytb) haplotypes within 239 and 213 isolates from 3 Asian countries. Phylogenetic tree topologies were presented high-level confidence values for the 2 major branches of 2 Spirometra species containing S. erinaceieuropaei and S. decipiens, and S. decipiens sub-clades including all sequences registered as S. erinaceieuropaei in cox1 and cytb genes. These results indicated that mitochondrial haplotypes of S. erinaceieuropaei and S. decipiens were found in the 3 Asian countries.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode with m.3243A>G variant involving the cerebellum and basal ganglia

  • Chungmo Koo;Jaejin Yang;Jeong Rye Kim;Jeesuk Yu
    • Journal of Genetic Medicine
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    • 제21권1호
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    • pp.36-40
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    • 2024
  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome is a maternally inherited mitochondrial disorder that usually affects the cerebral cortex and prevents high-energy demands from being met. Herein, we present the case of a male patient who rapidly developed multiple seizures, headaches, and altered mentality accompanied by severe metabolic acidosis and lactic acidosis. Initially, a brain imaging study confirmed stroke-like lesions (SLLs) only in the cerebellum. During follow-up, newly developed SLLs with lactic acidosis were observed in the basal ganglia (BG), cerebellum, and occipital lobe. The m.3243A>G variant had been found in the patient and MELAS was diagnosed, despite the BG and cerebellum being atypical locations for SLLs in MELAS. Since most cases of m.3243A>G variant MELAS show SLLs in the cerebral cortex, this case is unusual considering the location of the lesion. We emphasize that in the case of lactic acidosis accompanied by neurological symptoms, such as seizures, as in this case, MELAS should be included in the differential diagnosis, even if SLLs are observed in areas other than the cerebral cortex.

렘수면중 심한 저산소혈증을 보인 사립체근병증 1례 (A Case of Mitochondrial Myopathy Showing Severe Hypoxemia during REM Sleep)

  • 김주상;김성경;이상학;안중현;김치홍;문화식
    • 수면정신생리
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    • 제14권1호
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    • pp.49-53
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    • 2007
  • 사립체근병증은 운동시 근력약화와 같은 경한 증상에서 부터 중추신경계 질환으로 조기 사망에 이르기까지 돌연변이의 정도에 따라서 다양한 증상를 나타내는 질환이다. 그러므로 질환이 의심되는 경우 반드시 조직검사를 고려하여야 한다. 사립체근병증이 있더라도 다른 증상이 없이 무호흡 증후군이나 저환기 증후군의 형태로 처음 진단되는 경우가 드물지만, 사립체근병증이 진단된 후에는 폐기능 검사를 통해 질환의 진행에 대한 예측이 필요하며, 호흡 부전이 발생할 가능성이 높은 경우 비침습적기계환기를 통해 환자를 치료 할 수 있다. 저자들은 초기 중추성 수면 무호흡 증후군으로 오인되었다가 저환기 증후군으로 진단하고, 원인질환으로 사립체근병증을 진단하였으며, 비침습적 기계환기를 통해 성공적으로 치료하여 추적관찰 중인 1례를 경험하였기에 보고하는 바이다.

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Identification of causative mutations in patients with Leigh syndrome and MERRF by mitochondrial DNA-targeted next-generation sequencing

  • Hong, Hyun Dae;Kim, Eunja;Nam, Soo Hyun;Yoo, Da Hye;Suh, Bum Chun;Choi, Byung-Ok;Chung, Ki Wha
    • Journal of Genetic Medicine
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    • 제12권2호
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    • pp.109-117
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    • 2015
  • Purpose: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. Materials and Methods: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). Results: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. Conclusion: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.

Alterations of Antioxidant Status and Mitochondrial Succinate Dehydrogenase Activity in the Liver of Wistar Strain Albino Rats Treated with by Ethanol Extracts of Annona senegalensis Pers (Annonaceae) Stem Bark

  • Adisa, Rahmat Adetutu;Kolawole, Naimat;Sulaimon, Lateef A.;Brai, Bathlomew;Ijaola, Abraham
    • Toxicological Research
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    • 제35권1호
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    • pp.13-24
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    • 2019
  • Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The $LD_{50}$ value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.