Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling.
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 degrees C) or hypothermia (33 degrees 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.
Yang
Dan
D
Department of Pathology, Institute of Basic Medical Sciences, Beijing, China.
Guo
Shubin
S
Zhang
Tianpeng
T
Li
Huihua
H
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007036:Hypothermia, Induced; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D013696:Temperature
D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D054638:Dual Specificity Phosphatase 1