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Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling
Authors:Dan Yang  Shubin Guo  Tianpeng Zhang
Institution:a Department of Pathology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing 100005, China
b Department of Acute Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
Abstract:Hypothermia is the most effective means of protecting the brain, heart and other organs during ischemia/reperfusion (I/R) injury. However, the precise mechanisms for hypothermia to inhibit I/R-induced endothelial cell apoptosis are not fully understood. In the present study, human umbilical endothelial cells (HUVECs) were exposed to ischemia followed by reperfusion under normothermia (37 °C) or hypothermia (33 °C). Our results showed that hypothermia markedly reduced I/R-induced endothelial cell apoptosis, the expression of cleaved caspase-3 and PARP. Moreover, hypothermia markedly reversed I/R-induced activation of Fas/caspase-8, the increase of Bax and decrease of Bcl-2. Furthermore, hypothermia inhibited JNK1/2 activation via MKP-1 induction. Together, these data demonstrate that hypothermia represses I/R-induced endothelial cell apoptosis by inhibiting both extrinsic- and intrinsic-dependent apoptotic pathways and activation of JNK1/2.
Keywords:Hypothermia  Endothelial cell  Ischemia/reperfusion  Apoptosis  Signaling pathway
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