tailieunhanh - Báo cáo khoa học: CREB and cAMP response element-mediated gene expression in the ischemic brain

Cerebral ischemia triggers robust phosphorylation of cAMP response ele-ment-binding protein (CREB) and CRE-mediated gene expression in neu-rons. Glutamate receptor activation and subsequent calcium influx may activate CREB shortly after ischemia. | ễFEBS Journal MINIREVIEW CREB and cAMP response element-mediated gene expression in the ischemic brain Kazuo Kitagawa Stroke Division Department of Neurology Osaka University Graduate Schoolof Medicine Suita Japan Keywords Bcl-2 brain protection cerebral ischemia CREB glutamate hypoxia ischemic tolerance neurogenesis neuron phosphodiesterase inhibitor Correspondence K. Kitagawa Stroke Division Department of Neurology Osaka University Graduate Schoolof Medicine 2-2 Yamadaoka Suita Osaka 565-0871 Japan Fax 81 6 6878 6574 Tel 81 6 6879 3634 E-mail kitagawa@ Received 29 January 2007 revised 5 May 2007 accepted 15 May 2007 doi Cerebral ischemia triggers robust phosphorylation of cAMP response element-binding protein CREB and CRE-mediated gene expression in neurons. Glutamate receptor activation and subsequent calcium influx may activate CREB shortly after ischemia. CREB activation leads to expression of genes encoding neuroprotective molecules such as the antiapoptotic protein Bcl-2 and contributes to survival of neurons after ischemic insult. Recent studies have suggested that CREB may be involved in acquisition of ischemic tolerance a phenomenon that occurs after sublethal ischemic stress. CREB activation is also involved in the survival of newborn neurons in the dentate gyrus of the hippocampus after ischemia. Therefore CREB-related therapeutics may be promising for brain protection and endogenous neurogenesis and could promote functional recovery in ischemic stroke patients. This minireview summarizes our current understanding for the role of CREB in regulating CRE-mediated gene expression during cerebral ischemia. Introduction The cAMP response element-binding protein CREB is necessary for proliferation growth survival and differentiation of all types of cells and is expressed ubiquitously in all organs. In the brain the CREB and CRE-mediated system is involved in memory learning and synaptic transmission as