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Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin.
Ding, Mingge; Ning, Jiao; Feng, Na; Li, Zeyang; Liu, Zhenhua; Wang, Yuanbo; Wang, Yueming; Li, Xing; Huo, Cong; Jia, Xin; Xu, Rong; Fu, Feng; Wang, Xiaoming; Pei, Jianming.
Afiliación
  • Ding M; Department of Geriatrics, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, China.
  • Ning J; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Feng N; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Li Z; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Liu Z; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Wang Y; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Wang Y; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Li X; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Huo C; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Jia X; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Xu R; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Fu F; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Wang X; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  • Pei J; Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
J Pineal Res ; 64(1)2018 Jan.
Article en En | MEDLINE | ID: mdl-29024001
Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction. However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post-traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to 5-minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model. Melatonin was administrated intraperitoneally 5 minute after MT. Mitochondrial morphology, myocardial injury, and cardiac function were determined in vivo. There was smaller size of mitochondria and increased number of mitochondria per µm2 in the hearts after MT when the secondary myocardial injury was induced. Melatonin treatment at the dose of 30 mg/kg reduced serine 616 phosphorylation of Drp1 and inhibited mitochondrial Drp1 translocation and mitochondrial fission in the hearts of rats subjected to MT, which contributed to the reduction of myocardial injury and the improvement of cardiac function. In vitro, H9c2 cells cultured in 20% traumatic plasma (TP) for 12 hour showed enhanced mitochondrial fission, mitochondrial membrane potential (∆Ψm) loss, mitochondrial cytochrome c release, and decreased mitochondrial complex I-IV activities. Pretreatment with melatonin (100 µmol/L) efficiently inhibited TP-induced mitochondrial fission, ∆Ψm loss, cytochrome c release, and improved mitochondrial function. Melatonin's protective effects were attributed to its role in suppressing plasma TNF-α overproduction, which was responsible for Drp1-mediated mitochondrial fission. Taken together, our results demonstrate for the first time that abnormal mitochondrial dynamics is involved in post-traumatic cardiac dysfunction. Melatonin has significant pharmacological potential in protecting against MT-induced cardiac dysfunction by preventing excessive mitochondrial fission.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dinaminas / Melatonina Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dinaminas / Melatonina Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido