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J Neurochem ; 157(3): 574-585, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33289070

RESUMEN

Nuclear factor (NF)-κB-mediated neuroinflammation is an important mechanism of intracerebral hemorrhage (ICH)-induced neurotoxicity. Silent information regulator 1 (SIRT1) plays a multi-protective effect in a variety of diseases by deacetylating and inhibiting NF-κB/p65. However, the role of SIRT1 in brain damage following ICH remains unclear. We hypothesized that SIRT1 can protect against ICH-induced brain damage by inhibiting neuroinflammation through deacetylating NF-κB/p65. The ICH model was induced in vivo (with collagenase) and in vitro (with hemoglobin). Resveratrol and Ex527 were administered to activate or inhibit SIRT1, respectively. Western blot, immunohistochemistry, and immunofluorescence assays were performed to detect the expression of SIRT1 and p65. Enzyme-linked immunosorbent assays (ELISAs) were used to explore tumor necrosis factor (TNF)-α and interleukin (IL)-1ß release. The neurological score, brain water content, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and brain hemoglobin content were determined to evaluate the neuroprotective effect of SIRT1. SIRT1 expression was decreased, whereas the level of acetylated p65 (Ac-p65) was elevated after ICH in vivo. Moreover, hemoglobin treatment decreased the expression of SIRT1 in vitro. Activation of SIRT1 by resveratrol had a neuroprotective effect, along with decreased levels of Ac-p65, IL-1ß, TNF-α, and apoptosis after ICH. The effect of resveratrol was abolished by the SIRT1 inhibitor Ex527. Our results are consistent with the hypothesis that SIRT1 exerts a neuroprotective effect after ICH by deacetylating p65 to inhibit the NF-κB-dependent inflammatory response.


Asunto(s)
Hemorragia Cerebral/tratamiento farmacológico , Fármacos Neuroprotectores , Sirtuina 1/genética , Factor de Transcripción ReIA/efectos de los fármacos , Acetilación , Animales , Apoptosis/efectos de los fármacos , Hemorragia Cerebral/inducido químicamente , Colagenasas , Encefalitis/tratamiento farmacológico , Encefalitis/patología , Hemoglobinas , Inyecciones Intraventriculares , Interleucina-1beta/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Cultivo Primario de Células , Resveratrol/uso terapéutico , Sirtuina 1/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
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