Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. Export

@article{kim07induction, abstract = {High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant nonhistone DNA-binding protein. Recently, it was found to act as a cytokine-like mediator of delayed endotoxin lethality and of acute lung injury. Previously, we reported that HMGB1 is massively released extracellularly and plays a cytokine-like function in the postischemic brain. In the present study, we examined the expression profile and cellular distribution of HMGB1 in rat brain after transient focal cerebral ischemia. The expression of HMGB1 in infarction areas in the ipsilateral sides gradually declined over 2 days after 1 hr of middle cerebral artery occlusion (MCAO) to below the basal level. However, after 3 days of reperfusion, HMGB1 level increased to above the basal level, especially in infarction cores, and this delayed induction was then maintained for several days. Immunohistochemistry using a polyclonal antibody against HMGB1 revealed its detailed expression pattern and subcellular localization in the postischemic brain. HMGB1 was found to be widely expressed throughout the normal brain and to be localized to the nuclei of almost all neurons and oligodendrocyte-like cells. After 1 hr of MCAO, HMGB1 immediately translocated from the neuron nuclei to the cytoplasm and subsequently was depleted from neurons during the excitotoxicity-induced acute damaging process. Moreover, beginning 2 days after reperfusion, HMGB1 was notably induced in activated microglia, astrocytes, and in microvascular structures, and these delayed gradual inductions were sustained for several days. These findings suggest that HMGB1 functions as a cytokine-like mediator in a paracrine and autocrine manner in the postischemic brain. (c) 2007 Wiley-Liss, Inc.}, address = {Department of Anatomy and Center for Advanced Medical Education (BK21 project), Inha University School of Medicine, Inchon, Korea.}, author = {Kim, Jung-Bin B. and Lim, Chae-Moon M. and Yu, Young-Mi M. and Lee, Ja-Kyeong K.}, citeulike-article-id = {1971807}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/jnr.21555}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17975839}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17975839}, day = {1}, doi = {10.1002/jnr.21555}, issn = {0360-4012}, journal = {J Neurosci Res}, keywords = {hmgb-1}, month = {November}, posted-at = {2007-11-24 10:47:20}, priority = {2}, title = {Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain.}, url = {http://dx.doi.org/10.1002/jnr.21555}, year = {2007} }

TY - JOUR ID - kim07induction L3 - citeulike-article-id:1971807 N2 - High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant nonhistone DNA-binding protein. Recently, it was found to act as a cytokine-like mediator of delayed endotoxin lethality and of acute lung injury. Previously, we reported that HMGB1 is massively released extracellularly and plays a cytokine-like function in the postischemic brain. In the present study, we examined the expression profile and cellular distribution of HMGB1 in rat brain after transient focal cerebral ischemia. The expression of HMGB1 in infarction areas in the ipsilateral sides gradually declined over 2 days after 1 hr of middle cerebral artery occlusion (MCAO) to below the basal level. However, after 3 days of reperfusion, HMGB1 level increased to above the basal level, especially in infarction cores, and this delayed induction was then maintained for several days. Immunohistochemistry using a polyclonal antibody against HMGB1 revealed its detailed expression pattern and subcellular localization in the postischemic brain. HMGB1 was found to be widely expressed throughout the normal brain and to be localized to the nuclei of almost all neurons and oligodendrocyte-like cells. After 1 hr of MCAO, HMGB1 immediately translocated from the neuron nuclei to the cytoplasm and subsequently was depleted from neurons during the excitotoxicity-induced acute damaging process. Moreover, beginning 2 days after reperfusion, HMGB1 was notably induced in activated microglia, astrocytes, and in microvascular structures, and these delayed gradual inductions were sustained for several days. These findings suggest that HMGB1 functions as a cytokine-like mediator in a paracrine and autocrine manner in the postischemic brain. (c) 2007 Wiley-Liss, Inc. JF - J Neurosci Res SN - 0360-4012 AD - Department of Anatomy and Center for Advanced Medical Education (BK21 project), Inha University School of Medicine, Inchon, Korea. TI - Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. KW - hmgb-1 AU - Kim, Jung-Bin AU - Lim, Chae-Moon AU - Yu, Young-Mi AU - Lee, Ja-Kyeong PY - 2007/11/01/ UR - http://dx.doi.org/10.1002/jnr.21555 ER -