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Sulfide catabolism ameliorates hypoxic brain injury.
Marutani, Eizo; Morita, Masanobu; Hirai, Shuichi; Kai, Shinichi; Grange, Robert M H; Miyazaki, Yusuke; Nagashima, Fumiaki; Traeger, Lisa; Magliocca, Aurora; Ida, Tomoaki; Matsunaga, Tetsuro; Flicker, Daniel R; Corman, Benjamin; Mori, Naohiro; Yamazaki, Yumiko; Batten, Annabelle; Li, Rebecca; Tanaka, Tomohiro; Ikeda, Takamitsu; Nakagawa, Akito; Atochin, Dmitriy N; Ihara, Hideshi; Olenchock, Benjamin A; Shen, Xinggui; Nishida, Motohiro; Hanaoka, Kenjiro; Kevil, Christopher G; Xian, Ming; Bloch, Donald B; Akaike, Takaaki; Hindle, Allyson G; Motohashi, Hozumi; Ichinose, Fumito.
Afiliação
  • Marutani E; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Morita M; Harvard Medical School, Boston, MA, USA.
  • Hirai S; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Kai S; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Grange RMH; Harvard Medical School, Boston, MA, USA.
  • Miyazaki Y; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Nagashima F; Harvard Medical School, Boston, MA, USA.
  • Traeger L; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Magliocca A; Harvard Medical School, Boston, MA, USA.
  • Ida T; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Matsunaga T; Harvard Medical School, Boston, MA, USA.
  • Flicker DR; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Corman B; Harvard Medical School, Boston, MA, USA.
  • Mori N; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Yamazaki Y; Harvard Medical School, Boston, MA, USA.
  • Batten A; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Li R; Harvard Medical School, Boston, MA, USA.
  • Tanaka T; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Ikeda T; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Nakagawa A; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Atochin DN; Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
  • Ihara H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Olenchock BA; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Shen X; Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Nishida M; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Hanaoka K; Harvard Medical School, Boston, MA, USA.
  • Kevil CG; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Xian M; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Bloch DB; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Akaike T; Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems & Center for Novel Science Initiatives, National Institutes of Natural Sciences, Okazaki, Japan.
  • Hindle AG; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Motohashi H; Harvard Medical School, Boston, MA, USA.
  • Ichinose F; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Nat Commun ; 12(1): 3108, 2021 05 25.
Article em En | MEDLINE | ID: mdl-34035265
ABSTRACT
The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfidequinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinona Redutases / Encéfalo / Lesões Encefálicas / Sulfeto de Hidrogênio Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinona Redutases / Encéfalo / Lesões Encefálicas / Sulfeto de Hidrogênio Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos