Signal transducers and activators of transcription: STATs-mediated mitochondrial neuroprotection.
Cerebral ischemia is defined as little or no blood flow in cerebral circulation, characterized by low tissue oxygen and glucose levels, which promotes neuronal mitochondria dysfunction leading to cell death. A strategy to counteract cerebral ischemia-induced neuronal cell death is ischemic preconditioning (IPC). IPC results in neuroprotection, which is conferred by a mild ischemic challenge prior to a normally lethal ischemic insult. Although many IPC-induced mechanisms have been described, many cellular and subcellular mechanisms remain undefined. Some reports have suggested key signal transduction pathways of IPC, such as activation of protein kinase C epsilon, mitogen-activated protein kinase, and hypoxia-inducible factors, that are likely involved in IPC-induced mitochondria mediated-neuroprotection. Moreover, recent findings suggest that signal transducers and activators of transcription (STATs), a family of transcription factors involved in many cellular activities, may be intimately involved in IPC-induced ischemic tolerance. In this review, we explore current signal transduction pathways involved in IPC-induced mitochondria mediated-neuroprotection, STAT activation in the mitochondria as it relates to IPC, and functional significance of STATs in cerebral ischemia.
Lin
Hung Wen
HW
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida 33101, USA.
Thompson
John W
JW
Morris
Kahlilia C
KC
Perez-Pinzon
Miguel A
MA
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019194:Ischemic Preconditioning; D008928:Mitochondria / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D050791:STAT Transcription Factors