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Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage.
Suzuki, Takehiro; Yamaguchi, Hiroaki; Kikusato, Motoi; Hashizume, Osamu; Nagatoishi, Satoru; Matsuo, Akihiro; Sato, Takeya; Kudo, Tai; Matsuhashi, Tetsuro; Murayama, Kazutaka; Ohba, Yuki; Watanabe, Shun; Kanno, Shin-Ichiro; Minaki, Daichi; Saigusa, Daisuke; Shinbo, Hiroko; Mori, Nobuyoshi; Yuri, Akinori; Yokoro, Miyuki; Mishima, Eikan; Shima, Hisato; Akiyama, Yasutoshi; Takeuchi, Yoichi; Kikuchi, Koichi; Toyohara, Takafumi; Suzuki, Chitose; Ichimura, Takaharu; Anzai, Jun-Ichi; Kohzuki, Masahiro; Mano, Nariyasu; Kure, Shigeo; Yanagisawa, Teruyuki; Tomioka, Yoshihisa; Toyomizu, Masaaki; Tsumoto, Kohei; Nakada, Kazuto; Bonventre, Joseph V; Ito, Sadayoshi; Osaka, Hitoshi; Hayashi, Ken-Ichi; Abe, Takaaki.
Afiliación
  • Suzuki T; Divisions of Nephrology, Endocrinology, and Vascular Medicine and Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
  • Yamaguchi H; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan;
  • Kikusato M; Animal Nutrition, Life Sciences, Graduate School of Agricultural Science.
  • Hashizume O; Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan;
  • Nagatoishi S; Department of Bioengineering, University of Tokyo, Tokyo, Japan;
  • Matsuo A; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Sato T; Departments of Molecular Pharmacology.
  • Kudo T; Primetech Co. Ltd., Tokyo, Japan;
  • Matsuhashi T; Pediatrics and.
  • Murayama K; Division of Biomedical Measurements and Diagnostics and.
  • Ohba Y; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Watanabe S; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Kanno S; Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer.
  • Minaki D; Graduate School of Pharmaceutical Sciences, and.
  • Saigusa D; Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan;
  • Shinbo H; Kanagawa Children's Medical Center, Yokohama, Japan;
  • Mori N; Internal Medicine and Rehabilitation Science, and.
  • Yuri A; Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan;
  • Yokoro M; Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, Nishinomiya, Japan;
  • Mishima E; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Shima H; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Akiyama Y; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Takeuchi Y; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Kikuchi K; Divisions of Nephrology, Endocrinology, and Vascular Medicine and Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Japan;
  • Toyohara T; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Suzuki C; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Ichimura T; Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
  • Anzai J; Graduate School of Pharmaceutical Sciences, and.
  • Kohzuki M; Internal Medicine and Rehabilitation Science, and.
  • Mano N; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan;
  • Kure S; Pediatrics and.
  • Yanagisawa T; Departments of Molecular Pharmacology.
  • Tomioka Y; Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan;
  • Toyomizu M; Animal Nutrition, Life Sciences, Graduate School of Agricultural Science.
  • Tsumoto K; Department of Bioengineering, University of Tokyo, Tokyo, Japan;
  • Nakada K; Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan;
  • Bonventre JV; Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
  • Ito S; Divisions of Nephrology, Endocrinology, and Vascular Medicine and.
  • Osaka H; Division of Pediatrics, Jichi Medical University, Tochigi, Japan; and.
  • Hayashi K; Department of Biochemistry, Okayama University of Science, Okayama, Japan.
  • Abe T; Divisions of Nephrology, Endocrinology, and Vascular Medicine and Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan; takaabe@med.tohoku.ac.j
J Am Soc Nephrol ; 27(7): 1925-32, 2016 07.
Article en En | MEDLINE | ID: mdl-26609120
ABSTRACT
Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid-resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin-induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I-IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Miocitos Cardíacos / Miocitos del Músculo Liso / Ácidos Indolacéticos / Túbulos Renales / Mitocondrias Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Miocitos Cardíacos / Miocitos del Músculo Liso / Ácidos Indolacéticos / Túbulos Renales / Mitocondrias Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2016 Tipo del documento: Article