کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8841290 | 1614711 | 2017 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sonic hedgehog induces GLT-1 degradation via PKC delta to suppress its transporter activities
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کلمات کلیدی
ASPPKC deltaGLT-1PKCδPKCSMOCYCphorbol 12-myristate 13-acetatePMA - LDC هاMTT - MTTSTP - PTSAstrocytes - آستروسیتaspartate - آسپارتاتThiazolyl blue tetrazolium bromide - تترازولیم برومید تیزولیل آبیShh - خیرcyclopamine - سیکلوپامینSmoothened - صافsonic hedgehog - صدای جیر جیرWAY - مسیرtransferrin receptor - گیرنده انتقالین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
GLT-1 is mainly expressed in astrocytes and has a crucial role in glutamate uptake. Sonic hedgehog (SHH) can inhibit glutamate uptake and its pathway is activated in many brain diseases related with glutamate excitotoxicity. However, whether SHH regulates GLT-1 to affect glutamate uptake is not clear. Here, we use pharmacological and genetic methods to show that SHH induces GLT-1 degradation in astrocytes in a manner that is dependent on PKC delta (PKCδ) to regulate GLT-1 activities. GLT-1 protein levels are reduced as early as 2â¯hs in astrocytes after incubation with SHH, whereas its mRNA levels are not changed. This reduction is recapitulated when astrocytes are transfected with SmoA1, a constitutively active form of Smoothened (Smo), the mediator of SHH pathway. The reduction of GLT-1 and inhibition of aspartate current are not observed when staurosporine (STP) and BisindolylmaleimideII (BisII), agents known as PKC inhibitors, are present. Further, when PKCδ is knocked down in astrocytes, SHH cannot reduce GLT-1 protein levels. Therefore, SHH induces degradation of GLT-1 through PKCδ to regulate its activities.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 365, 4 December 2017, Pages 217-225
Journal: Neuroscience - Volume 365, 4 December 2017, Pages 217-225
نویسندگان
Yuqing Wang, Shanshan Lu, Zhongwei Qu, Lin Wu, Yizheng Wang,