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Ophiopogonin D attenuates doxorubicin-induced autophagic cell death by relieving mitochondrial damage in vitro and in vivo.
Zhang, Ying-Yu; Meng, Chen; Zhang, Xin-Mu; Yuan, Cai-Hua; Wen, Ming-Da; Chen, Zhong; Dong, Da-Chuan; Gao, Yan-Hong; Liu, Chang; Zhang, Zhao.
Afiliação
  • Zhang YY; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Meng C; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Zhang XM; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Yuan CH; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Wen MD; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Chen Z; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Dong DC; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Gao YH; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Liu C; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
  • Zhang Z; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China (Y.-Y.Z., C.M., C.-H.Y., M.-D.W., Z.C., D.-C.D., Y.-H.G., C.L., Z.Z.); Department of Clinical Medicine, Changchun Medical College, Changchun, China (Y.-Y.Z.); and Depart
J Pharmacol Exp Ther ; 352(1): 166-74, 2015 Jan.
Article em En | MEDLINE | ID: mdl-25378375
ABSTRACT
It has been reported that ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against doxorubicin (DOX)-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of reactive oxygen species (ROS) in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio, and upregulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine. In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by antioxidative effects through downregulating the expression of both phosphorylated c-Jun N-terminal kinase and extracellular signal-regulated kinase. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Saponinas / Autofagia / Espirostanos / Doxorrubicina / Citoproteção / Mitocôndrias Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Saponinas / Autofagia / Espirostanos / Doxorrubicina / Citoproteção / Mitocôndrias Idioma: En Ano de publicação: 2015 Tipo de documento: Article