• 제목/요약/키워드: Mitochondrial fragmentation

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Comprehensive overview of the role of mitochondrial dysfunction in the pathogenesis of acute kidney ischemia-reperfusion injury: a narrative review

  • Min-Ji Kim;Chang Joo Oh;Chang-Won Hong;Jae-Han Jeon
    • Journal of Yeungnam Medical Science
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    • 제41권2호
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    • pp.61-73
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    • 2024
  • Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

Cytotoxic Activity from Curcuma zedoaria Through Mitochondrial Activation on Ovarian Cancer Cells

  • Shin, Yujin;Lee, Yongkyu
    • Toxicological Research
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    • 제29권4호
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    • pp.257-261
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    • 2013
  • ${\alpha}$-Curcumene is one of the physiologically active components of Curcuma zedoaria, which is believed to perform anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the mechanism of the apoptotic effect of ${\alpha}$-curcumene on the growth of human overian cancer, SiHa cells. Upon treatment with ${\alpha}$-curcumene, cell viability of SiHa cells was inhibited > 73% for 48 h incubation. ${\alpha}$-Curcumene treatment showed a characteristic nucleosomal DNA fragmentation pattern and the percentage of sub-diploid cells was increased in a concentration-dependent manner, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of ${\alpha}$-curcumene, which mediates cell death. These results suggest that the apoptotic effect of ${\alpha}$-curcumene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c.

Up-regulation of Cyelin A-Cdk2 activity is associated with depolarization of mitochondrial membrane potential during apoptosis of human hepatoma SK-HEP1 cells induced by treatment with panaxadiol

  • Park, Byoung-Duck;Jin, Ying-Hua;Yim, Hyung-Shin;Lee, Seung-Ki
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.167.1-167.1
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    • 2003
  • Here we show that panaxadiol, a ginseng saponin with a dammarane skeleton, induces acute apoptotic cell death in human hepatoma SK-HEP-1 cells as evidenced by analysis of DNA fragmentation, caspase activation, and changes in cell morphology. The kinetic study showed that panaxadiol-induced apoptosis is associated with depolarization of mitochondrial membrane potential and cytochrome c release. Sequential activations of caspases-depolarization of mitochondrial membrane potential and cytochrome c release. Sequential activations of caspases-9, and -3, or -7, but not of caspase 8 coincide well in a time dependent manner with mitochondrial membrane depolarization and cytochrome c release from mitochondria during apoptosis of SK-HEP-1 cells induced by treatment with panaxadiol. (omitted)

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Relationship between the nucleolar cycle and chromatoid body formation in the spermatogenesis of $Phrynops$ $geoffroanus$ (Reptilia Testudines)

  • Peruquetti, Rita L.;Taboga, Sebastiao R.;Cabral, Silvia R.;De Oliveira, Classius;Azeredo-Oliveira, Maria T.
    • Animal cells and systems
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    • 제16권2호
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    • pp.104-113
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    • 2012
  • The nucleolus is a distinct nuclear territory involved in the compartmentalization of nuclear functions. There is some evidence of a relationship between nuclear fragmentation during spermatogenesis and chromatoid body (CB) formation. The CB is a typical cytoplasmic organelle of haploid germ cells, and is involved in RNA and protein accumulation for later germ-cell differentiation. The goal of this study was to qualitatively and quantitatively describe the nucleolar cycle during the spermatogenesis of $Phrynops$ $geoffroanus$ (Reptilia Testudines), and compare this nucleolar fragmentation with CB formation in this species through the use of cytochemical and ultrastructural analysis. Qualitative analysis showed a fragmentation of the nuclear material after pachytene of the first meiotic division in the primary spermatocytes. Quantitative analysis of the nucleolar cycle revealed a significant difference in the number of nucleoli and in the size of the nucleolus between spermatogonia and early spermatids. Using ultrastructural analysis, we recorded the beginning of the CB formation process in the cytoplasm of primary spermatocytes at the same time as when nuclear fragmentation occurs. In the cytoplasm of primary spermatocytes, the CB was observed in association with mitochondrial aggregates and the Golgi complex. In the cytoplasm of early spermatids, the CB was observed in association with lipid droplets. In conclusion, our data show that the nucleolus plays a role in the CB formation process. During spermatogenesis of $P.$ $geoffroanus$, the CB is involved in some important biological processes, including acrosome formation and mitochondrial migration to the spermatozoon tail and middle piece region.

Induction of Apoptotic Cell Death by a Ceramide Analog in PC-3 Prostate Cancer Cells

  • Oh, Ji-Eun;So, Kwang-Sup;Lim, Se-Jin;Kim, Mie-Young
    • Archives of Pharmacal Research
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    • 제29권12호
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    • pp.1140-1146
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    • 2006
  • Ceramide analogs are potential chemotherapeutic agents. We report that a ceramide analog induces apoptosis in human prostate cancer cells. The ceramide analog induced cell death through an apoptotic mechanism, which was demonstrated by DNA fragmentation, the cleavage of poly ADP ribose polymerase (PARP), and a loss of membrane asymmetry. Treating the cells with ceramide analog resulted in the release of various proapoptotic mitochondrial proteins including cytochrome c and Smac/DIBLO into the cytosol, and a decrease in the mitochondrial membrane potential. In addition, the ceramide analog decreased the phospho-Akt and phospho-Bad levels. The expression of the antiapoptotic Bcl-2 decreased slightly with increasing Bax to Bcl-2 ratio. These results suggest that the ceramide analog induces apoptosis by regulating multiple signaling pathways that involve the mitochondrial pathway.

녹용 에탄올 분획이 생쥐의 T-Lymphocyte에 미치는 영향 (Effect of Ethyl Alcohol Fraction of Cervus nippon on Mouse T-Lymphocyte)

  • 서정숙;오찬호;염정열;은재순;전길자
    • 생약학회지
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    • 제29권4호
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    • pp.312-317
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    • 1998
  • In this study, the effect of 70% ethyl alcohol fraction of Cervus nippon(CN-E) on mouse T-lymphocyte was investigated in vivo. The administration of CN-E(100 mg/kg) enhanced the proliferation of thymocytes, the population of $CD4^+CD8^-$ single-positive cells and the production of $interferon-{\gamma}$ in thymocytes and splenocytes. The administration of CN-E did not induce DNA fragmentation and reduce mitochondrial transmembrane potential in thymocytes. These results indicate that the CN-E contams a stimulative component on the proliferation of thymocytes, the population of $T_H$ cells and the production of $interferon-{\gamma}$ in T-lymphocytes.

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Ectopic Expression of Mitochondria Endonuclease Pnu1p from Schizosaccharomyces pombe Induces Cell Death of the Yeast

  • Oda, Kaoru;Kawasaki, Nami;Fukuyama, Masashi;Ikeda, Shogo
    • BMB Reports
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    • 제40권6호
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    • pp.1095-1099
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    • 2007
  • Endonuclease G (EndoG) is a mitochondrial non-specific nuclease that is highly conserved among the eukaryotes. Although the precise role of EndoG in mitochondria is not yet known, the enzyme is released from the mitochondria and digests nuclear DNA during apoptosis in mammalian cells. Schizosaccharomyces pombe has an EndoG homolog Pnu1p (previously named SpNuc1) that is produced as a precursor protein with a mitochondrial targeting sequence. During the sorting into mitochondria the signal sequence is cleaved to yield the functionally active endonuclease. From the analogy to EndoG, active extramitochondrial Pnu1p may trigger cell killing by degrading nuclear DNA. Here, we tested this possibility by expressing a truncated Pnu1p lacking the signal sequence in the extramitochondrial region of pnu1-deleted cells. The truncated Pnu1p was localized in the cytosol and nuclei of yeast cells. And ectopic expression of active Pnu1p led to cell death with fragmentation of nuclear DNA. This suggests that the Pnu1p is possibly involved in a certain type of yeast cell death via DNA fragmentation. Although expression of human Bak in S. pombe was lethal, Pnu1p nuclease is not necessary for hBak-induced cell death.

과루인이 자궁경부암세포의 성장억제 및 세포고사에 미치는 영향 (Growth Arrest and Apoptosis of Human Uterine Cervical Carcinoma Cells Induced by Trichosanthes Semen Extract)

  • 이정구;김연희;이동녕;김형준
    • 동의생리병리학회지
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    • 제19권4호
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    • pp.965-972
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    • 2005
  • To investigate the effects of Trichosanthes semen extract on the growth and apoptosis of human uterine cervical carcinoma cells. Effects of Trichosanthes semen extract on the growth of ME-180 cells were assayed by MTT assay. Apoptosis induced by Trichosanthes semen extract was detected by fluorescent microscopy, DNA fragmentation analysis and flow cytometry. Caspase-3 and caspase-8 activities were assayed. Trichosanthes semen extract induced ME-180 cells to die in a dose- and time-dependent manner. ME-180 cells treated with Trichosanthes semen extract exhibited typical characteristics of apoptosis. The population of Sub-G1 cells increased significantly, and the cells represented the reduced size, condensed chromatin and apoptotic bodies. They showed the decreased mitochondrial membrane potential and increased activities of caspase-3 and caspase-8. The results suggest that Trichosanthes semen extract induced ME-180 cell apoptosis and the activation of caspase and mitochondrial pathway were involved in the process of Trichosanthes semen extract-induced apoptosis.

Population genetic structure based on mitochondrial DNA analysis of Ikonnikov's whiskered bat (Myotis ikonnikovi-Chiroptera: Vespertilionidae) from Korea

  • Park, Soyeon;Noh, Pureum;Choi, Yu-Seong;Joo, Sungbae;Jeong, Gilsang;Kim, Sun-Sook
    • Journal of Ecology and Environment
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    • 제43권4호
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    • pp.454-461
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    • 2019
  • Background: Ikonnikov's whiskered bat (Myotis ikonnikovi) is found throughout the Korean Peninsula, as well as in Kazakhstan, Russia, Mongolia, China, and Japan. It is small-sized and primarily inhabits old-growth forests. The decrease and fragmentation of habitats due to increased human activity may influence the genetic structure of bat populations. This study was designed to elucidate the population genetic structure of M. ikonnikovi using mitochondrial genes (cytochrome oxidase I and cytochrome b). Results: The results showed that M. ikonnikovi populations from Korea have high genetic diversity. Although genetic differentiation was not detected for the COI gene, strong genetic differentiation of the Cytb gene between Mt. Jeombong and Mt. Jiri populations was observed. Moreover, the results indicated that the gene flow of the maternal lineage may be limited. Conclusions: This study is the first to identify the genetic population structure of M. ikonnikovi. We suggest that conservation of local populations is important for sustaining the genetic diversity of the bat, and comprehensive studies on factors causing habitat fragmentation are required.

Analysis of Membrane Integrity, DNA Fragmentation and Mitochondrial Function in Pig Spermatozoa Sorted by Flowcytometer

  • Kim, In-Cheul;Han, Deug-Woo;Lee, Sung-Won;Ryu, Jae-Weon;Choi, Eun-Ji;Son, Jung-Ho
    • Reproductive and Developmental Biology
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    • 제32권2호
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    • pp.123-126
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    • 2008
  • The objective of this study was to determine the potential hazardous effects of sorting process by flowcytometry on the quality of boar spermatozoa by flowcytometer. Freshly collected boar semen was diluted and divided into two groups; control none sorted and sorted. Sperms in sorted group were processed with flowcytometer for cell sorting with $100\;{\mu}M$ nozzle under the 20 psi pressure. Measurements on each parameter were made at two time points, 0hr (right after sorting) and 24 hr post sorting. Although there was a tendency of lower viability in sorted group than none sorted control group, the percentage of live cells in control ($75.83{\pm}6.92\;&\;59.53{\pm}10.34$) was not significantly different from sorted ($59.70{\pm}7.37\;&\;43.97{\pm}3.76$) at both 0 and 24 hr post sorting. However, sorted sperm showed significantly lower mitochondrial function compared to the control at both 0 h ($79.37{\pm}3.22\;vs.\;63.50{\pm}10.05$) and 24 hr ($67.27{\pm}3.22$ vs. $46.97{\pm}5.37$) time points (p<0.007). Sperm DNA fragmentation rate was significantly lower in control ($22.0{\pm}7.04$) than that of sorted ($32.27{\pm}7.49$) at 24 hr time point (p<0.0002). Taken together, these data suggested thatsorting process by flowcytometer may have influenced sperm motility rather than viability. Also high speed sperm sorting by flowcytometer has significant effects on DNA fragmentation on elapsed time after sorting.