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SIRT1 activation by minocycline on regulation of microglial polarization homeostasis.
Wu, Ling-Hsuan; Huang, Bor-Ren; Lai, Sheng-Wei; Lin, Chingju; Lin, Hsiao-Yun; Yang, Liang-Yo; Lu, Dah-Yuu.
Afiliación
  • Wu LH; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
  • Huang BR; Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
  • Lai SW; School of Medicine, Tzu Chi University, Hualien, Taiwan.
  • Lin C; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
  • Lin HY; Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan.
  • Yang LY; Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
  • Lu DY; Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan.
Aging (Albany NY) ; 12(18): 17990-18007, 2020 Sep 23.
Article en En | MEDLINE | ID: mdl-33021962
Sirtuin 1 (SIRT1) has been reported to be involved in the mechanisms underlying longevity and has also been indicated as a valuable regulator of age-related neurological disorders. Some natural products increase SIRT1 activity and stimulate deacetylation of various proteins. In the present study, SIRT1 overexpression by genetic modification or treatment with SIRT1 activators significantly inhibited the secretion of nitric oxide and expression of inducible nitric oxide synthase, cyclooxygenase 2, and proinflammatory mediator-interleukin 1ß-in microglia. SIRT1 activation also decreased the levels of K379 acetyl-p53 and the protein inhibitor of activated Stat 1 expression in microglial cells. In addition, it dramatically promoted M2 polarization of microglia, which enhanced cell motility and altered phagocytic ability. We also used minocycline, a well-known inhibitor of microglial activation, to study the mechanism of SIRT1 signaling. Minocycline treatment decreased neuroinflammatory responses and promoted M2 polarization of microglia. It also reduced the acetyl-p53 level in the brain tissues in an inflammatory mouse model. Our findings demonstrated that SIRT1 participates in the maintenance of microglial polarization homeostasis and that minocycline exerts regulatory effects on SIRT1 activation. Therefore, our results indicate that SIRT1 activation may be a useful therapeutic target for the treatment of neuroinflammation-associated disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos