کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2200322 1551279 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Autophagy regulates intracerebral hemorrhage induced neural damage via apoptosis and NF-κB pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Autophagy regulates intracerebral hemorrhage induced neural damage via apoptosis and NF-κB pathway
چکیده انگلیسی


• Inhibition of autophagy provide neuroprotective effect in ICH model.
• This protective role may be provided by inhibiting apoptotic activation.
• Inhibition of autophagy may suppress the activation of the NF-κB pathway.
• Both in vivo and in vitro experiment were adopted to verify.

Autophagy can be a pro-survival or a pro-death mechanism depending on the context. The role of autophagy in intracerebral hemorrhage (ICH) remains elusive. In this study, in vivo and in vitro experiments have been carried out to investigate the role of autophagy after ICH. Collagenase-induced ICH model in mouse was made for in vivo experiments. Primary cortical neurons cultures were exposed to hemin to mimic ICH in vitro. 3-Methyladenine (3-MA) and rapamycin (RAP) were administrated both in vivo and in vitro. We first measured brain water content and cell death after ICH in model. Expression of LC3, p62/SQSTM1 (p62), Beclin1, Caspase3 and Bcl-2, which have been found related to autophagy and apoptosis, were assessed both in vivo and in vitro. Furthermore, NF-κB was detected to explore the potential mechanisms. We found brain edema in ICH model in mouse and the number of Propidium Iodide (PI)-positive cells both in vivo and in vitro were decreased by 3-MA pretreated. Simultaneously, both in vivo and in vitro, 3-MA significantly decreased the expression of LC3-II and Beclin-1, and maintained p62 at high level after ICH. Furthermore, pretreatment with 3-MA downregulated the level of cleaved caspase-3 but upregulated the Bcl-2 level. Conversely, RAP pretreatment reversed all these results above. These data indicated that autophagy activation may deprave ICH induced brain injury in ICH model and neuro-damage may be related to regulating of NF-κB pathway and thereby promote inflammation and apoptosis, thus might provide novel therapeutic interventions for ICH.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 96, June 2016, Pages 100–112
نویسندگان
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