کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964566 | 1058558 | 2007 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1/2 on ischemic brain injury
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کلمات کلیدی
COX IVSP600125RTKPIP3MOPSpKaPIP2ERKNACJnkPI3K3-(N-morpholino)propanesulfonic acid - 3- (N-مورفولینو) پروپان سولفونیک اسیدc-Jun N-terminal kinase - C-Jun N-terminal kinaseI/R - I / RMAPK - MAPKN-acetylcysteine - N-استیل سیستئینAkt - آکتischemia/reperfusion - ایسکمی / رپرفیوژنCerebral ischemia - ایسکمی مغزیANOVA - تحلیل واریانس Analysis of varianceRTK, Receptor tyrosine kinase - تیروزین کینازهای گیرنده ایcytochrome c oxidase subunit IV - سیتوکروم C اکسیداز Subunit IVextracellular signal regulated kinase - سیگنال خارج سلولی kinase را تنظیم می کندphosphatase and tensin homolog deleted on chromosome 10 - فسفاتاز و هومولوگ تنسین حذف شده در کروموزوم 10phosphatidylinositol-4,5-bisphosphate - فسفاتیدیلینستول-4،5-بیسفسفاتphosphatidylinositol-3,4,5-trisphosphate - فسفاتیدیلینواستیل 3،4،5-تری فسفاتphosphoinositide 3-kinase - فسفینوزیتید 3-کینازprotein kinase A - پروتئین کیناز Amitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPten - ژن PTEN
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Increasing evidence suggests that the Bcl-2 family proteins play pivotal roles in regulation of the mitochondria cell-death pathway on transient cerebral ischemia. Bad, a BH3-only proapoptotic Bcl-2 family protein, has been shown to be phosphorylated extensively on serine by kinds of kinases. However, the exact mechanisms of the upstream kinases in regulation of Bad signaling pathway remain unknown. Here, we reported that Bad could be phosphorylated not only by Akt1 but also by JNK1/2 after transient global ischemia in rat hippocampal CA1 region. Our data demonstrated that Akt1 mediated the phosphorylation of Bad at serine 136, which increased the interaction of serine 136-phosphorylated Bad with 14-3-3 proteins and prevented the dimerization of Bad with Bcl-Xl, inhibited the release of cytochrome c to the cytosol and the death effector caspase-3 activation, leading to the survival of neuron. In contrast, JNK1/2 induced the phosphorylation of Bad at a novel site of serine 128 after brain ischemia/reperfusion, which inhibited the interaction of PI3K/Akt-induced serine 136-phosphorylated Bad with 14-3-3 proteins, thereby promoted the apoptotic effect of Bad. In addition, activated Akt1 inhibited the activation of Bad(S128) through downregulating JNK1/2 activation, thus inhibiting JNK-mediated Bad apoptosis pathway. Furthermore, the fate of cell to survive or to die was determined by a balance between prosurvival and proapoptotic signals. Taken together, our studies reveal that Bad phosphorylation at two distinct sites induced by Akt1 and JNK1/2 have opposing effects on ischemic brain injury, and present the possibility of Bad as a potential therapeutic target for stroke treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 19, Issue 9, September 2007, Pages 1844-1856
Journal: Cellular Signalling - Volume 19, Issue 9, September 2007, Pages 1844-1856
نویسندگان
Xiao-Tian Wang, Dong-Sheng Pei, Jing Xu, Qiu-Hua Guan, Ya-Feng Sun, Xiao-Mei Liu, Guang-Yi Zhang,