Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling

Yang, Dan; Guo, Shubin; Zhang, Tianpeng; Li, Huihua

doi:10.1016/j.febslet.2009.07.006

« Previous Next »FEBS Letters
Volume 583, Issue 15 , Pages 2500-2506, 6 August 2009

Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling

Edited by Jesus Avila

Dan Yang
- Department of Pathology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing 100005, China
- Dan Yang and Shubin Guo contributed equally to this work.
Shubin Guo
- Department of Acute Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
- Dan Yang and Shubin Guo contributed equally to this work.
Tianpeng Zhang
- Department of Pathology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing 100005, China
Huihua Li
- Department of Pathology and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Beijing 100005, China
- Corresponding author. Fax: +86 10 6529 6494.

Received 15 May 2009; received in revised form 30 June 2009; accepted 9 July 2009. published online 13 July 2009.

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.