Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways

Neuroscience
Q-H GuanG-Y Zhang

Abstract

Our previous studies and the others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. Here we reported that Tat-JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1), a smaller 11-mer peptide corresponding to residues 153-163 of murine JIP-1 conjugated to Tat peptide, perturbed the assembly of JIP-1-JNK3 complexes, thus inhibiting the activation of JNK3 induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. As a result, Tat-JBD diminished the increased phosphorylation of c-Jun (a nuclear substrate of JNK) and the increased expression of Fas ligand induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. At the same time, through inhibiting phosphorylation of Bcl-2 (a cytosolic target of JNK) and the release of Bax from Bcl-2/Bax dimers, Tat-JBD attenuated Bax translocation to mitochondria and the release of cytochrome c induced by ischemia/reperfusion. Furthermore, the activation of caspase3 and hydrolyzation of poly-ADP-ribose-polymerase induced by brain ischemia/reperfusion were also significantly suppressed by preinfusion of the peptide Tat-JBD. Importantly, Tat-JBD showed neuroprotective effects on is...Continue Reading

References

May 1, 1979·Stroke; a Journal of Cerebral Circulation·W A Pulsinelli, J B Brierley
Sep 22, 1999·Molecular and Cellular Biology·J YasudaR J Davis
Jan 5, 2000·The Journal of Biological Chemistry·S KharbandaD Kufe
Apr 27, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·G CaoJ Chen
Sep 20, 2001·Genes & Development·A J WhitmarshR J Davis
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·N PlesnilaM A Moskowitz
Jun 5, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Elaine A Irving, Mark Bamford
Aug 30, 2002·The Journal of Biological Chemistry·Xiao-Ming YinJun Chen
Feb 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kui Lei, Roger J Davis
Jun 24, 2003·Neuron·Girish V PutchaEugene M Johnson
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Chia-Yi KuanPasko Rakic
Dec 12, 2003·Drug News & Perspectives·Zhen ZhengMidori A Yenari
Jun 23, 2004·The Journal of Biological Chemistry·Renae K BarrMarie A Bogoyevitch
Feb 18, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yanqin GaoJun Chen

❮ Previous
Next ❯

Citations

Sep 6, 2013·Journal of Cardiovascular Translational Research·Rong JinGuohong Li
Mar 29, 2011·ACS Chemical Biology·Tamer S KaoudKevin N Dalby
Apr 1, 2009·The Journal of Biological Chemistry·Ginny G FaríasNibaldo C Inestrosa
Apr 29, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Takayuki KatoSeiichi Kitagawa
Apr 23, 2011·Journal of Neurotrauma·Woo Hyeun KangBarclay Morrison
Sep 7, 2012·PloS One·Melanie ClarkeShawn Hayley
Mar 18, 2009·Molecular and Cellular Neurosciences·Yi Zhao, Thomas Herdegen
Mar 1, 2008·Neuropharmacology·Kristian P DoyleMary P Stenzel-Poore
Dec 21, 2007·Advanced Drug Delivery Reviews·Sadamitsu Asoh, Shigeo Ohta
Oct 30, 2007·Biochimica Et Biophysica Acta·Marie A Bogoyevitch, Peter G Arthur
Feb 17, 2007·Current Opinion in Cell Biology·Claire R Weston, Roger J Davis
Jan 25, 2007·Neurosurgery Clinics of North America·Elena I Fomchenko, Eric C Holland
Dec 3, 2008·Journal of Neurochemistry·Vanessa GinetAnita C Truttmann
Jan 15, 2008·Journal of Neuroscience Research·Nik SaweHeng Zhao
Oct 19, 2011·Journal of Neurochemistry·Anne VaslinPeter G H Clarke
Jan 19, 2012·Journal of Neurochemistry·Zeng-Jin YangRaymond C Koehler
Oct 17, 2014·Journal of Neurochemistry·Chung-Ching ChioHuei-Sheng Huang
Oct 14, 2008·Biochimica Et Biophysica Acta·Lorenzo GalluzziGuido Kroemer
Sep 25, 2016·Neurochemical Research·Hongjian LuJianbin Yang
Jun 23, 2009·Nature Reviews. Neuroscience·Lorenzo GalluzziGuido Kroemer
Nov 23, 2006·Physiology·Oksana Kaidanovich-Beilin, Hagit Eldar-Finkelman
Jun 24, 2019·The FEBS Journal·Emilie HollvilleMohanish Deshmukh

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis