The Neuroprotective Effect of Losartan through Inhibiting AT1/ASK1/MKK4/JNK3 Pathway Following Cerebral I/R in Rat Hippocampal CA1 Region
作者： Tian-Ling Zhang , Jian-Liang Fu , Zhi Geng , Jia-Jun Yang , Xiao-Jiang Sun
DOI: 10.1111/CNS.12015
关键词: Endocrinology 、 Angiotensin II receptor type 1 、 Receptor 、 Neuroprotection 、 ASK1 、 Internal medicine 、 Angiotensin II 、 Protein kinase A 、 Mitogen-activated protein kinase 、 Chemistry 、 Losartan
摘要: Summary Aims It has been well documented that angiotensin II type 1 (AT1) receptor blockers (ARBs) are known to attenuate neural damage and the c-Jun N-terminal protein kinase 3 (JNK3) pathway caspase-3 signal involved in neuronal cell death following cerebral ischemia/reperfusion (I/R). In this study, we first showed losartan could protect neurons against I/R-induced injury. Methods Cerebral ischemia model was induced by four-vessel occlusion. Antisense oligodeoxynucleotides (ODNs) AT1 were used detect whether implicated I/R. Immunoprecipitation (IP) immunoblotting (IB) interactions between β-arrestin-2 AT1/apoptosis signal-regulating (ASK1)/MAP 4 (MKK4) signaling module I/R. Results First, decreased death. Second, depressed β-arrestin-2-assembled AT1/ASK1/MKK4 module. Third, activation of c-jun, JNK3, Bcl-2, release cytochrome c from mitochondria cytoplasm. Conclusion Taken together, I/R via inhibiting depressing c.
sci-hub.se 参考文章(35)
Roger J Davis, Signal transduction by the JNK group of MAP kinases. Cell. ,vol. 103, pp. 239- 252 ,(2000) , 10.1016/S0092-8674(00)00116-1
Joachim Schrader, Stephan Lüders, Anke Kulschewski, Jürgen Berger, Walter Zidek, Johannes Treib, Karl Einhäupl, Hans Christoph Diener, Peter Dominiak, The ACCESS Study: Evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors Stroke. ,vol. 34, pp. 1699- 1703 ,(2003) , 10.1161/01.STR.0000075777.18006.89
Eric Reiter, Robert J. Lefkowitz, GRKs and β-arrestins: roles in receptor silencing, trafficking and signaling Trends in Endocrinology and Metabolism. ,vol. 17, pp. 159- 165 ,(2006) , 10.1016/J.TEM.2006.03.008
Zhenglin Gu, Qian Jiang, Guangyi Zhang, c-Jun N-terminal kinase activation in hippocampal CA1 region was involved in ischemic injury. Neuroreport. ,vol. 12, pp. 897- 900 ,(2001) , 10.1097/00001756-200104170-00006
Yu-Lan Niu, Chong Li, Guang-Yi Zhang, Blocking Daxx trafficking attenuates neuronal cell death following ischemia/reperfusion in rat hippocampus CA1 region Archives of Biochemistry and Biophysics. ,vol. 515, pp. 89- 98 ,(2011) , 10.1016/J.ABB.2011.07.016
Shu-Qun Hu, Jie Zhu, Dong-Sheng Pei, Yan-Yan Zong, Jing-Zhi Yan, Xiao-Yu Hou, Guang-Yi Zhang, Overexpression of the PDZ1 domain of PSD-95 diminishes ischemic brain injury via inhibition of the GluR6·PSD-95·MLK3 pathway Journal of Neuroscience Research. ,vol. 87, pp. 3626- 3638 ,(2009) , 10.1002/JNR.22163
Scott M. DeWire, Seungkirl Ahn, Robert J. Lefkowitz, Sudha K. Shenoy, β-Arrestins and Cell Signaling Annual Review of Physiology. ,vol. 69, pp. 483- 510 ,(2007) , 10.1146/ANNUREV.PHYSIOL.69.022405.154749
DW Choi, Cerebral hypoxia: some new approaches and unanswered questions. The Journal of Neuroscience. ,vol. 10, pp. 2493- 2501 ,(1990) , 10.1523/JNEUROSCI.10-08-02493.1990
K.A. DeFea, J. Zalevsky, M.S. Thoma, O. Déry, R.D. Mullins, N.W. Bunnett, beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. Journal of Cell Biology. ,vol. 148, pp. 1267- 1282 ,(2000) , 10.1083/JCB.148.6.1267
Hyun-Woo Kim, Kyoung-Joo Cho, Su Kyoung Lee, Gyung W. Kim, Apoptosis signal-regulating kinase 1 (Ask1) targeted small interfering RNA on ischemic neuronal cell death. Brain Research. ,vol. 1412, pp. 73- 78 ,(2011) , 10.1016/J.BRAINRES.2011.07.018