title: Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal Syndrome.
abstract: Experimental evidence has clarified distant organ dysfunctions induced by AKI. Crosstalk between the kidney and heart, which has been recognized recently as cardiorenal syndrome, appears to have an important role in clinical settings, but the mechanisms by which AKI causes cardiac injury remain poorly understood. Both the kidney and heart are highly energy-demanding organs that are rich in mitochondria. Therefore, we investigated the role of mitochondrial dynamics in kidney-heart organ crosstalk. Renal ischemia reperfusion (IR) injury was induced by bilateral renal artery clamping for 30 min in 8-week-old male C57BL/6 mice. Electron microscopy showed a significant increase of mitochondrial fragmentation in the heart at 24 h. Cardiomyocyte apoptosis and cardiac dysfunction, evaluated by echocardiography, were observed at 72 h. Among the mitochondrial dynamics regulating molecules, dynamin-related protein 1 (Drp1), which regulates fission, and mitofusin 1, mitofusin 2, and optic atrophy 1, which regulate fusion, only Drp1 was increased in the mitochondrial fraction of the heart. A Drp1 inhibitor, mdivi-1, administered before IR decreased mitochondrial fragmentation and cardiomyocyte apoptosis significantly and improved cardiac dysfunction induced by renal IR. This study showed that renal IR injury induced fragmentation of mitochondria in a fission-dominant manner with Drp1 activation and subsequent cardiomyocyte apoptosis in the heart. Furthermore, cardiac dysfunction induced by renal IR was improved by Drp1 inhibition. These data suggest that mitochondrial fragmentation by fission machinery may be a new therapeutic target in cardiac dysfunction induced by AKI.
authors: Department of Nephrology and Endocrinology.
authors: Maki
authors: M
authors: Sumida
authors: Department of Nephrology and Endocrinology, Department of Emergency and Critical Care Medicine, kdoi-tky@umin.ac.jp.
authors: Kent
authors: K
authors: Doi
authors: Department of Nephrology and Endocrinology.
authors: Emi
authors: E
authors: Ogasawara
authors: Department of Nephrology and Endocrinology.
authors: Tetsushi
authors: T
authors: Yamashita
authors: Department of Nephrology and Endocrinology, 22nd Century Medical and Research Center, and.
authors: Yoshifumi
authors: Y
authors: Hamasaki
authors: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; and.
authors: Taro
authors: T
authors: Kariya
authors: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; and.
authors: Eiki
authors: E
authors: Takimoto
authors: Department of Emergency and Critical Care Medicine.
authors: Naoki
authors: N
authors: Yahagi
authors: Department of Nephrology and Endocrinology.
authors: Masaomi
authors: M
authors: Nangaku
authors: Department of Nephrology and Endocrinology, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Tokyo, Japan.
authors: Eisei
authors: E
authors: Noiri
mesh_terms: D000208:Acute Disease; D000818:Animals; D059347:Cardio-Renal Syndrome / Q000503:physiopathology*; D034281:Dynamins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063154:Mitochondrial Dynamics
chemical_list: C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: acute renal failure; apoptosis; cardiovascular; mitochondria
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