N-Acetylcysteine inhibit the translocation of mixed lineage kinase-3 from cytosol to plasma membrane during transient brain ischemia in rat hippocampus

• Published in: Neuroscience letters Vol. 391; no. 1; pp. 38 - 42
• Main Authors: Pei, Dong-Sheng, Guan, Qiu-Hua, Sun, Ya-Feng, Zhang, Qing-Xiu, Xu, Tian-Le, Zhang, Guang-Yi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 31.12.2005; Elsevier
• Subjects: Acetylcysteine - administration & dosage; Animals; Biological and medical sciences; Brain Ischemia - metabolism; Cell Membrane - drug effects; Cell Membrane - metabolism; Cerebral ischemia; Cytosol - drug effects; Cytosol - metabolism; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; Male; MAP Kinase Kinase Kinases - metabolism; Medical sciences; Mitogen-Activated Protein Kinase Kinase Kinase 11; Mixed lineage kinase-3 (MLK3); N-Acetylcysteine (NAC); Neurology; Postsynaptic density protein 95 (PSD-95); Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Cerebral ischemia; N-Acetylcysteine (NAC); Mixed lineage kinase-3 (MLK3); Postsynaptic density protein 95 (PSD-95); Rat; Enzyme; Transferases; Rodentia; Central nervous system; Acetylcysteine; Cardiovascular disease; Cytosol; Protein; Encephalon; Vertebrata; Mammalia; Ischemia; Kinase; Animal; Plasma membrane; Postsynaptic density; Hippocampus
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2005.08.029

Mixed lineage kinase-3 (MLK3) is a recently described member of the MLK subfamily of Ser/Thr protein kinases that interacts with mitogen-activated protein kinase (MAPK) pathways. In this study, we investigated the translocation of MLK3 during transient cerebral ischemia in rat hippocampus. Transient brain ischemia was induced by the four-vessel occlusion in Sprague–Dawley rats. Our data show that MLK3 can translocate from cytosolic fraction to the membrane fraction during ischemia and the increased MLK3 in the membrane fraction bind to postsynaptic density protein 95 (PSD-95). The antioxidant N-acetylcysteine (NAC) could inhibit the translocation of MLK3 from cytosolic fraction to the membrane fraction and decrease the interactions of MLK3 and PSD-95 in the membrane fraction. Consequently, these results indicate that reactive oxygen species (ROS) was closely associated with MLK3 translocation induced by transient global ischemia in rat hippocampus.