Cell-cycle regulators are involved in transient cerebral ischemia induced neuronal apoptosis in female rats

详细信息	查看全文 | 推荐本文 |

• 作者：Yi Wen ; Shaohua Yang ; Ran Liu and James W. Simpkins
• 关键词：Ischemia ; Stroke ; Cell cycle ; Retinoblastoma protein ; Cdk 4 and BrdU ; Cyclin D1 ; Proliferating cell nuclear antigen
• 刊名：FEBS Letters
• 出版年：2005
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：2005
• 卷：579
• 期：21
• 页码：4591-4599
• 文件大小：671 K

摘要

Recent evidence indicates that cell-cycle regulating proteins are involved in apoptotic process in post-mitotic neurons. In this study, we examined cell-cycle regulators for G₁/S cell-cycle progression after a transient focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. In the cerebral frontoparietal cortex, we observed a marked induction of Cyclin D1 (a coactivator of Cdks), and proliferating cell nuclear antigen (PCNA), together with upregulated Cdk kinase activities. This process is accompanied with multiple phosphorylation of retinoblastoma (Rb) protein at Cdk phosphorylation sites in neurons from the ischemic cortex. We further examined DNA synthesis by the incorporation of BrdU, a nucleotide analog that incorporates into newly synthesized DNA. Within 24-h of reperfusion after 60-min occlusion, substantial BrdU-positive neurons were observed in the ischemic cortex. Inhibition of Cdk4 activity during this ischemia/reperfusion is highly neuroprotective. These results suggest that ischemia/reperfusion cerebral damage induces signalings at the G₁/S cell-cycle transition, and may constitute a critical step in the neuronal apoptotic pathway in ischemia/reperfusion induced neuronal damage.