• Title/Summary/Keyword: (sub)mitochondria

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Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential

  • Yang, Shasha;Li, Xiangdan;Dou, Haowen;Hu, Yulai;Che, Chengri;Xu, Dongyuan
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.3
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    • pp.223-232
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    • 2020
  • Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway

  • Jo, Hantae;Oh, Jeong-Hyun;Park, Dong-Wook;Lee, Changho;Min, Churl K.
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.96-104
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    • 2020
  • Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψm), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψm, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

Prophylactic role of Korean Red Ginseng in astrocytic mitochondrial biogenesis through HIF-1α

  • Park, Jinhong;Lee, Minjae;Kim, Minsu;Moon, Sunhong;Kim, Seunghee;Kim, Sueun;Koh, Seong-Ho;Kim, Young-Myeong;Choi, Yoon Kyung
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.408-417
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    • 2022
  • Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O2 consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O2 consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

Ultrastructural Study on the Maturation of Oocyte in the African Giant Snail, Achatina fulica (아프리카 왕달팽이 (Achatina fulica) 난모세포 성숙에 관한 미세구조)

  • Chang, Nam-Sub;Han, Jong-Min
    • Applied Microscopy
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    • v.30 no.4
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    • pp.367-376
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    • 2000
  • The observation using an electron microscope shows that the maturation of the oocyte of African giant snail, Achatina fulica, proceeds over three stages. The oocyte of stage 1 is a small elliptic cell $(220\times400{\mu}m)$ whose light nucleoplasm contains two nucleoli. In its cytoplasm, a number of mitochondria, rough endoplasmic reticula, and ribosomes are found, while yolk granules are not. The nucleus of the oocyte of stage 2 is relatively large in comparison with the volume of cytoplasm, and contains one nucleolus. In the nuclear envelope comprising inner and outer double membrane, there are found a lot of nuclear pores for materials to pass through. A number of mitochondria, Golgi complex and lipid yolk granules appears in the cytoplasm, and proteinous yolk granules begin to form and mature in the vacuoles of various sizes ($0.8\sim3.0{\mu}m$ in diameter). The oocyte of stage 3 has an enlarged nucleolus. Material transportation through nuclear pore is not found any longer. The cytoplasm in this stage is filled with proteinous and lipid yolk granules. The microvilli are developed around the egg plasma membrane.

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Microstructural Characteristics of the Ordered and Disordered Leaves in Citrus junos Sieb.

  • Park, Min-Hee;Boo, Hee-Ock;Kim, Hong-Sub;Lee, Sook-Young
    • Plant Resources
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    • v.3 no.3
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    • pp.163-172
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    • 2000
  • We compared microstructural features of the ordered cell and disordered leaves in Citrus junos Sieb. by electron microscopy. In the cell of the ordered leaves, many chloroplasts and large vacuoles were particularly observed. Also a lot of vessel, companion cell and big nucleus were presented in vascular bundle regions. The mitochondria and the other organelles were interspersed among the chloroplasts in a thin, peripheral layer of cytoplasm. The chloroplast possessed typical grana and intergranal lamellae, numerous starch grains and a few small osmophilic globules. Besides, microbodies were closely associated with the mitochondria and the chloroplast. The process of the formation of the secondary cell wall from primary cell wall was observed the vessel elements, the tonoplast wall and the secondary cell wall. It was observed that the oil sac with the unique perfume distributed the adjacent cell wall. In the cell of disordered leaves, the all of the organelles were thrust toward the cell wall due to the fusion of vacuoles in the cells. It was observed that a lot of the very small particles spreaded in the cytoplasm. The loss of unique perfume of the leaves was resulted in the destruction of the oil sac. Also, there was not observed grana, lamellae, starch and osmophillic globules in the chloroplast. The small distributed organelles was not observed but the elongation of the cell wall was proceed no longer. Therefore, the plasma membrane diverged from the cell wall. All of organelles in the cell had poor function and deformation. A massive vacuole was fulfilled in single cell and the vacuole contains a lot of large and small particles. The organelles were presented on the side of the cell wall according to the enlargement of vacuole and they were observed to be breakdown.

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Adverse Effect of Superovulation Treatment on Maturation, Function and Ultrastructural Integrity of Murine Oocytes

  • Lee, Myungook;Ahn, Jong Il;Lee, Ah Ran;Ko, Dong Woo;Yang, Woo Sub;Lee, Gene;Ahn, Ji Yeon;Lim, Jeong Mook
    • Molecules and Cells
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    • v.40 no.8
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    • pp.558-566
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    • 2017
  • Regular monitoring on experimental animal management found the fluctuation of ART outcome, which showed a necessity to explore whether superovulation treatment is responsible for such unexpected outcome. This study was subsequently conducted to examine whether superovulation treatment can preserve ultrastructural integrity and developmental competence of oocytes following oocyte activation and embryo culture. A randomized study using mouse model was designed and in vitro development (experiment 1), ultrastructural morphology (experiment 2) and functional integrity of the oocytes (experiment 3) retrieved after PMSG/hCG injection (superovulation group) or not (natural ovulation; control group) were evaluated. In experiment 1, more oocytes were retrieved following superovulation than following natural ovulation, but natural ovulation yielded higher (p < 0.0563) maturation rate than superovulation. The capacity of mature oocytes to form pronucleus and to develop into blastocysts in vitro was similar. In experiment 2, a notable (p < 0.0186) increase in mitochondrial deformity, characterized by the formation of vacuolated mitochondria, was detected in the superovulation group. Multivesicular body formation was also increased, whereas early endosome formation was significantly decreased. No obvious changes in other microorganelles, however, were detected, which included the formation and distribution of mitochondria, cortical granules, microvilli, and smooth and rough endoplasmic reticulum. In experiment 3, significant decreases in mitochondrial activity, ATP production and dextran uptake were detected in the superovulation group. In conclusion, superovulation treatment may change both maturational status and functional and ultrastuctural integrity of oocytes. Superovulation effect on preimplantation development can be discussed.

Fungicidal activity of synthetic piericidin analogs as inhibitors of NADH-ubiquinone oxidoreductase on the respiratory chain (호습쇄의 NADH-ubiquinone oxidoreductase 저해제인 합성 piericidin유사체드르이 살균활성)

  • Chung, Kun-Hoe;Cho, Kwang-Yun;Takahashi, Nobutaka;Yoshida, Shigeo
    • Applied Biological Chemistry
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    • v.33 no.3
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    • pp.264-267
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    • 1990
  • Representative synthetic piericidin-like compounds, such as hydroxypyridine and hydroxyquinoline derivatives, which showed high inhibition activity against NADH-ubiquinone oxidoreductase on the respiratory chain revealed good fungicide activity. Especially, hydrolrypyridine ones showed high activity against rice blast (Pyricularia oryzae) and barley powdery mildew (Erysiphe graminis).

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The coordinated regulation of mitochondrial structure and function by Drp1 for mitochondrial quality surveillance

  • Cho, Hyo Min;Sun, Woong
    • BMB Reports
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    • v.52 no.2
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    • pp.109-110
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    • 2019
  • Mitochondrial morphology is known to be continuously changing via fusion and fission, but it is unclear what the biological importance of this energy-consuming process is and how it develops. Several data have suggested that mitochondrial fission executed by Drp1 is necessary to select out a damaged spot from the interconnected mitochondrial network, but the precise mechanism for the recognition and isolation of a damaged sub-mitochondrial region during mitochondrial fission is yet unclear. Recently, Cho et al. found that the mitochondrial membrane potential (MMP) is transiently reduced by the physical interaction of Drp1 and mitochondrial Zinc transporter, Zip1, at the fission site prior to the typical mitochondrial division, and we found that this event is essential for a mitochondrial quality surveillance. In this review, Cho et al. discuss the role of a mitochondrial fission in the mitochondrial quality surveillance system.

A New Histone Deacetylase Inhibitor, MHY4381, Induces Apoptosis via Generation of Reactive Oxygen Species in Human Prostate Cancer Cells

  • Richa, Sachan;Dey, Prasanta;Park, Chaeun;Yang, Jungho;Son, Ji Yeon;Park, Jae Hyeon;Lee, Su Hyun;Ahn, Mee-Young;Kim, In Su;Moon, Hyung Ryong;Kim, Hyung Sik
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.184-194
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    • 2020
  • Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC50 value of MHY4381 was lower in DU145 cells (IC50=0.31 µM) than in LNCaP (IC50=0.85 µM) and PC-3 cells (IC50=5.23 µM). In addition, the IC50 values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

Spermiogenesis in the Red-hacked Vole, Clethrionomys rufocanus regulus (한국산 대륙밭쥐(Clethrionomys rufocanus regulus)의 정자변태)

  • 손성원;이정훈
    • Biomedical Science Letters
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    • v.2 no.1
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    • pp.57-69
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    • 1996
  • To examine the process of spermiogenesis in the Korean red-backed vole, Clethrionomys rufocanus regulus, the seminiferous epithelium in the testis, was studied by trasmission electron microscopy, and the following results were obtained based on the morphological characteristics of cell differentiation. 1. According to the fine structural differentiation, spermiogenesis was divided into Golgi, cap, acrosome, maturation and spermiation phases. Besides, these phases were sub-divided into two steps : early and late phases respectively, Thus, the spermiogenesis of Clethrionomys rufocanus regulus was divided into a total of ten steps. 2. In the changes of the chromatin, the chromatin granules began to be condenced in the late Golgi phase, regularizated at maturation phases, and a perfect nucleus of sperm was formed at the spermiation phases. 3. The sperm head had the falciform, and the formative period of sperm tail began to be develop in the early Golgi phase and completed at the spermiation phases. 4. In the morphological features of spermiation phases, the spermatid of early spermiation phase was divided into three types : (1) A-type spermatid contained cytoplasmic droplets in the neck region and middle piece, and the mitochondria was irregular, and arranged around the axoneme. (2) B-type contained cytoplasmic droplet in the middle piece only, and the mitochondria are arranged the center of axoneme regularly, and (3) In the C-type spermatid, the arrangement of mitochondria was regular, and was contained cytoplasmic droplet in the neck region only. In the late spermiation phase, only the sperm head was surrounded by cytoplasm of Sertoli cell or the matured sperm just before the spermiation from the cytoplasm of Sertoli cell.

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