Your browser doesn't support javascript.
loading
Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats.
Zhang, Tongyu; Wu, Pei; Budbazar, Enkhjargal; Zhu, Qiquan; Sun, Chengmei; Mo, Jun; Peng, Jianhua; Gospodarev, Vadim; Tang, Jiping; Shi, Huaizhang; Zhang, John H.
Afiliação
  • Zhang T; From the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (T.Z., P.W., H.S.).
  • Wu P; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Budbazar E; From the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (T.Z., P.W., H.S.).
  • Zhu Q; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Sun C; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Mo J; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Peng J; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Gospodarev V; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Tang J; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Shi H; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
  • Zhang JH; Department of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Stroke ; 50(4): 978-988, 2019 04.
Article em En | MEDLINE | ID: mdl-30890112
Background and Purpose- Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of mitoquinone in mitophagy activation and oxidative stress-induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats. Methods- Endovascular perforation was used for SAH model of male Sprague-Dawley rats. Exogenous mitoquinone was injected intraperitoneally 1 hour after SAH. ML385, an inhibitor of Nrf2 (nuclear factor-E2-related factor 2), was given intracerebroventricularly 24 hours before SAH. Small interfering RNA for PHB2 (prohibitin 2) was injected intracerebroventricularly 48 hours before SAH. Nuclear, mitochondrial, and cytoplasmic fractions were gathered using nucleus and mitochondria isolation kits. SAH grade evaluation, short- and long- term neurological function tests, oxidative stress, and apoptosis measurements were performed. Pathway related proteins were investigated with Western blot and immunofluorescence staining. Results- Expression of Keap1 (Kelch-like epichlorohydrin-associated protein 1, 2.84× at 24 hours), Nrf2 (2.78× at 3 hours), and LC3II (light chain 3-II; 1.94× at 24 hours) increased, whereas PHB2 (0.46× at 24 hours) decreased after SAH compared with sham group. Mitoquinone treatment attenuated oxidative stress and neuronal death, both short-term and long-term. Administration of mitoquinone resulted in a decrease in expression of Keap1 (0.33×), Romo1 (reactive oxygen species modulator 1; 0.24×), Bax (B-cell lymphoma-2 associated X protein; 0.31×), Cleaved Caspase-3 (0.29×) and an increase in Nrf2 (2.13×), Bcl-xl (B-cell lymphoma-extra large; 1.67×), PINK1 (phosphatase and tensin-induced kinase 1; 1.67×), Parkin (1.49×), PHB2 (1.60×), and LC3II (1.67×) proteins compared with SAH+vehicle group. ML385 abolished the treatment effects of mitoquinone on behavior and protein levels. PHB2 small interfering RNA reversed the outcomes of mitoquinone administration through reduction in protein expressions downstream of PHB2. Conclusions- Mitoquinone inhibited oxidative stress-related neuronal death by activating mitophagy via Keap1/Nrf2/PHB2 pathway after SAH. Mitoquinone may serve as a potential treatment to relieve brain injury after SAH.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Hemorragia Subaracnóidea / Transdução de Sinais / Estresse Oxidativo / Fator 2 Relacionado a NF-E2 / Mitofagia / Proteína 1 Associada a ECH Semelhante a Kelch Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Hemorragia Subaracnóidea / Transdução de Sinais / Estresse Oxidativo / Fator 2 Relacionado a NF-E2 / Mitofagia / Proteína 1 Associada a ECH Semelhante a Kelch Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article