title: Rg1 prevents myocardial hypoxia/reoxygenation injury by regulating mitochondrial dynamics imbalance via modulation of glutamate dehydrogenase and mitofusin 2.
abstract: OBJECTIVE
  Mitochondrial dysfunction is a prominent feature of ischemia heart disease but the underlying mechanism of dynamics (fusion/fission) is still unclear. Here we investigated a novel function and underlying mechanism of Rg1 on an in vitro cardiomyocyte model of hypoxia/reoxygenation (H/R).
  
  
  METHODS
  Cellular cytotoxicity was evaluated by MTT, mitochondrial viable staining, and cardiac marker detection. Mitochondrial function was evaluated by ATP content measurement, MMP determination, ROS, OCR and ECAR assay. Mitochondrial dynamics was investigated by Live-cell imaging with time-lapse fluorescence microscopy and morphological features were evaluated by the high-content image analysis. Mitochondrial fusion and fission-related proteins, GDH were determined by Western blot, RT-PCR and immunofluorescence.
  
  
  RESULTS
  Rg1 moderated GDH dysregulation and then protected against H/R-induced cellular damage and mitochondrial dysfunction in a dose-dependent manner. Rg1 significantly increased mitochondrial length, reduced the number of cells with fragmented mitochondria and up-regulated the MFN2 expression finally leading to preventing the imbalance of mitochondrial dynamics following H/R. Knock-down of MFN2 by specific siRNA completely abolished the ability of Rg1 to cell survival by H/R.
  
  
  CONCLUSIONS
  Rg1 through modulation of GDH and MFN2 maintained mitochondrial dynamics that resulted in protection against H/R-induced cardiomyocyte injury. All these results put forward a new protective mechanism of Rg1 on the therapeutic potential in cardiac I/R disorders.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Gengting
authors.initials: G
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Xuecong
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Weixue
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Electronic address: pluo@must.edu.mo.
authors.forename: Pei
authors.initials: P
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Electronic address: hzhou@must.edu.mo.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D020558:GTP Phosphohydrolases; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D005969:Glutamate Dehydrogenase; D010749:Phosphoprotein Phosphatases; C413451:Ppp1r3a protein, rat; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat
keywords: Ginsenoside Rg1; Glutamate dehydrogenase; Ischemia heart disease; Mitochondrial dynamics; Mitofusin 2