کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7279696 | 1473899 | 2018 | 62 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Balasubramide derivative 3C modulates microglia activation via CaMKKβ-dependent AMPK/PGC-1α pathway in neuroinflammatory conditions
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کلمات کلیدی
LKB1Nuclear respiratory factor-2CaMKKβNRF-2PLLTMCAOSOD2EBSSUCP2NRF-1PGC-1αCBFTTCCCAECAAMPKPBSLPSJnkICAqPCR2,3,5-triphenyltetrazolium chloride - 2،3،5-trihenyltetrazolium chloride3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromideAMP-activated protein kinase - AMP-پروتئین کیناز فعال شده استc-Jun N-terminal kinase - C-Jun N-terminal kinaseERK1/2 - ERK1 / 2MAPK - MAPKMTT - MTTp38 MAPK - P38 MAPKQuantitative PCR - PCR کمیROS - ROSNeuroinflammation - التهاب عصبیtransient middle cerebral artery occlusion - انسداد شریان مغزی میانی متناوبELISA - تست الیزاcerebral blood flow - جریان خون مغزیSuperoxide dismutase 2 - سوکسوکس دیسموتاز 2Stroke - سکته مغزیexternal carotid artery - شریان کاروتید خارجیinternal carotid artery - شریان کاروتید داخلیcommon carotid artery - شریان کاروتید مشترکUncoupling Protein-2 - قطع پروتئین-2lipopolysaccharide - لیپوپلی ساکاریدPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریSprague-Dawley rats - موش Sprague-DawleySD rats - موش های صحرایی SDMicroglia - میکروگلیاهاmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenp38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38Poly-l-lysine - پلی-لیزینextracellular signal-regulated kinase 1/2 - کیناز 1/2 تنظیم سیگنال خارج سلولیliver kinase B1 - کیناز کیناز B1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Balasubramide derivative 3C modulates microglia activation via CaMKKβ-dependent AMPK/PGC-1α pathway in neuroinflammatory conditions Balasubramide derivative 3C modulates microglia activation via CaMKKβ-dependent AMPK/PGC-1α pathway in neuroinflammatory conditions](/preview/png/7279696.png)
چکیده انگلیسی
Neuroinflammation plays a vital role in the pathological process of cerebral ischemic stroke, but currently there is no effective treatment. After ischemia, microglia-produced proinflammatory mediator expression contributes to the aggravation of neuroinflammation, while anti-inflammatory activation of microglia develops an anti-neuroinflammatory effect via secretion of anti-inflammatory factor. Promoting the anti-inflammatory activation of microglia might be an effective treatment of stroke. Previously, we discovered one derivative of the natural product (+)-balasubramide, compound 3C, that exhibits a remarkably anti-neuroinflammatory effect in vitro with unknown mechanisms. Thus in this study, we aimed to clarify its molecular mechanisms and determine whether compound 3C has a neuroprotective effect after ischemia via regulation on microglial inflammation. We found that compound 3C promoted the anti-inflammatory mediator expression and reduced the proinflammatory mediator expression in LPS-stimulated BV2 cells and mouse primary microglia cells, which were reversed by AMP-activated protein kinase (AMPK) inhibition or AMPK upstream calmodulin-dependent protein kinase kinase beta (CaMKKβ) inhibition. Compound 3C also prevented LPS-stimulated JNK activation and enhanced PGC-1α activation in microglia, which was attenuated by AMPK inhibition. Additionally, compound 3C ameliorated depressive behaviors in LPS-induced neuroinflammatory mice by promoting the anti-inflammatory activation of microglia. Furthermore, we found that compound 3C markedly reduced brain infarct volume, improved the neurological deficit in rats with ischemia and reduced the activated microglia/macrophage cells in the ischemic area, which concomitantly enhanced the anti-inflammatory mediator expression. A mechanistic study showed that the compound 3C-mediated activation of CaMKKβ, AMPK and PGC-1α is involved in the anti-neuroinflammatory and neuroprotective effects of 3C in the brain of LPS-treated mice and ischemic rats. Taken together, our results show that compound 3C could suppress neuroinflammation in vitro and in vivo by modulating microglial activation state through the CaMKKβ-dependent AMPK/PGC-1α signaling pathway, and maybe further be developed as a promising new drug candidate for the treatment of brain disorders such as stroke associated with brain inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 67, January 2018, Pages 101-117
Journal: Brain, Behavior, and Immunity - Volume 67, January 2018, Pages 101-117
نویسندگان
Yunjie Wang, Wenchen Ruan, Junru Mi, Jingzi Xu, Haojie Wang, Zhengyu Cao, Juan M. Saavedra, Luyong Zhang, Hansen Lin, Tao Pang,