کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9954521 | 1551115 | 2018 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Deletion of Kir6.2/SUR1 potassium channels rescues diminishing of DA neurons via decreasing iron accumulation in PD
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کلمات کلیدی
IRPSSNCDATK-ATPMPTPFTLKirATP-sensitive potassiumGliDMT11-methyl-4-phenyl-1,2,3,6-tetrahydropyridine - 1-methyl-4-phenyl-1،2،3،6-tetrahydropyridineIron - آهنDopamine transporter - انتقال دهنده دوپامینParkinson's disease - بیماری پارکینسونinwardly rectifying potassium channel - درون کانال پتاسیم اصلاح شده استDopaminergic - دوپامینرژیکFerritin Light Chain - زنجیره فراترین نورDivalent metal transporter 1 - متال فلچر 1Substantia nigra compacta - متراکم توده سیاهiron-regulatory proteins - پروتئین های تنظیم کننده آهنglibenclamide - گلی بن کلامید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
ATP-sensitive potassium (K-ATP) channels express in the central nervous system extensively which coupling cell metabolism and cellular electrical activity. K-ATP channels in mature substantia nigra (SN) dopaminergic (DA) neurons are composed of inwardly rectifying potassium channel (Kir) subunit 6.2 and sulfonylurea receptor 1 (SUR1). Our previous study revealed that regulating K-ATP channel exerts the protective effect on DA neurons in a mouse model of Parkinson's disease (PD). However, the detailed mechanism underlying the role of Kir6.2/K-ATP remains unclear. In the present study, we found the deletion of Kir6.2 dramatically alleviated PD-like motor dysfunction of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model. We further found that Kir6.2 knockout selectively restored the reduction of both DA neuronal number and dopamine transmitter level in the nigrostriatal of MPTP-treated PD mice. To gain some understanding on the molecular basis of this effect, we focused on the regulation of Kir6.2 deletion on iron metabolism which is tightly associated with DA neuron damage. We found that Kir6.2 knockout suppressed the excessive iron accumulation in MPTP-treated mouse midbrain and inhibited the upregulation of ferritin light chain (FTL), which is a main intracellular iron storage protein. We probed further and found out that the deletion of Kir6.2 inhibited the excessive production of FTL via IRP-IRE regulatory system, and thereby protecting SN DA neurons against MPTP challenge. Our findings suggest that Kir6.2 plays a crucial role in the pathogenesis of PD and regulating Kir6.2/K-ATP channel may be a promising strategy for PD treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 92, October 2018, Pages 164-176
Journal: Molecular and Cellular Neuroscience - Volume 92, October 2018, Pages 164-176
نویسندگان
Qian Zhang, Chengwu Li, Ting Zhang, Yaping Ge, Xiaojuan Han, Sifan Sun, Jianhua Ding, Ming Lu, Gang Hu,