Activation of ASK1 during reperfusion of ischemic spinal cord

作者：Wang Peng; Cao Xiaojian; Nagel David J; Yin Guoyong^*

来源：Neuroscience Letters, 2007, 415(3): 248-252.

DOI：10.1016/j.neulet.2007.01.050

• ischemia
• reperfusion
• spinal cord
• 14-3-3
• ASK1

Apoptosis signal-regulating kinase I (ASK1) is a m togen -activated protein kinase kinase kinase (MAPKKK), which plays a pivotal role in cell apoptosis. To determine the mechanism of ASK1 induction during reperfusion of ischemic spinal tissue, we used a model of rabbit spinal cord ischemia and reperfusion. To assess the role of ASK1 in spinal cord ischemia-reperfusion injuries, we examined alterations in spinal tissue morphology, protein-protein interactions, and activation of key members of the ASKI-mediated signaling pathway. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. The phosphorylation levels of ASK1, JNK, and p38 were assessed by immunoblotting proteins from animals that received 30min of ischemia followed by I or 24h of reperfusion. We observed increased phosphorylation of ASK1, JNK, and p38 after reperfusing ischemic spinal cords. Immunohistochernical studies were performed to determine the cellular localization of phosphorylated ASKI (pASK1) and 14-3-3. Following reperfusion for 24h, we observed increased cytoplasmic localization of pASK1 and decreased cytoplasmic localization of 14-3-3. Immunoprecipitation analyses suggested that 14-3-3 dissociates from ASK1 during reperfusion of ischemic spinal cords. These results indicate that activation of ASK1 may play an important role in the apoptotic signaling mechanisms that occur in reperfused spinal cord injuries.

• 出版日期2007-3-30
• 单位南京医科大学