Neurochemical Research

, Volume 31, Issue 7, pp 967–974 | Cite as

Nitric Oxide Participates in the Induction of Brain Ischemic Tolerance via Activating ERK1/2 Signaling Pathways

  • Hui-Qing Liu
  • Wen-Bin Li
  • Qing-Jun Li
  • Min Zhang
  • Xiao-Cai Sun
  • Rong-Fang Feng
  • Xiao-Hui Xian
  • Shu-Qin Li
  • Jie Qi
  • Hong-Gang Zhao
Original Paper


The present study was undertaken to observe in vivo changes of expression and phosphorylation of ERK1/2 proteins during brain ischemic preconditioning and effects of inhibiting generation of nitric oxide (NO) on the changes to determine the role of ERKs in the involvement of NO participating in the acquired tolerance. Fifty-five Wistar rats were used. Brain ischemic preconditioning was performed with four-vessel occlusion for 3 min. Total ERK1/2 proteins and phospho-ERK1/2 in the CA1 hippocampus were assayed with Western immunoblot. Total ERK1/2 proteins did not change in period from 5 min to 5 days of reperfusion after preconditioning stimulus. While the level of phospho-ERK1/2 increased obviously to 223, 237, 300, 385 and 254% of sham level at times of 5 min, 2 h, 1, 3 and 5 days after preconditioning stimulus, respectively (< 0.01). Administration of L-NAME, an inhibitor of NO synthase, 30 min prior to preconditioning stimulus failed to induce change in total ERK1/2 proteins (> 0.05). However, phospho-ERK1/2 increased only to 138 and 176% of sham level at 2 h and 3 days after preconditioning stimulus, respectively, when animals were pretreated with L-NAME. The magnitudes of the increase were obviously low compared with those (237 and 385%) in animals untreated with L-NAME at corresponding time points (< 0.01), which indicated that phosphorylation of ERK1/2 normally induced by preconditioning stimulus was blocked apparently by administration of L-NAME. The results suggested that phosphorylation of ERK1/2, rather than synthesis of ERK1/2 proteins, was promoted in brain ischemic preconditioning, and that the promotion was partly mediated by NO signal pathway.


Brain ischemic preconditioning Extracellular signal-regulated protein kinase Nitric oxide Hippocampus Rat 



This work was supported by The Natural Science Foundation of Hebei province, P.R. China (No: 302494).


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Hui-Qing Liu
    • 2
  • Wen-Bin Li
    • 1
  • Qing-Jun Li
    • 1
  • Min Zhang
    • 1
  • Xiao-Cai Sun
    • 1
  • Rong-Fang Feng
    • 2
  • Xiao-Hui Xian
    • 1
  • Shu-Qin Li
    • 1
  • Jie Qi
    • 1
  • Hong-Gang Zhao
    • 3
  1. 1.Department of Pathophysiology, Institute of Basic MedicineHebei Medical UniversityShijiazhuangP.R. China
  2. 2.Department of NeurologyRen Min Hospital of Hebei provinceShijiazhuangP.R. China
  3. 3.Department of NeurobiologyXinxiang Medical CollegeXinxiang P.R. China

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