Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1

Jae Chul Lee, In Hye Kim, Joon Ha Park, Ji Hyeon Ahn, Jeong Hwi Cho, Geum Sil Cho, Hyun Jin Tae, Bai Hui Chen, Bing Chun Yan, Ki Yeon Yoo, Jung Hoon Choi, Choong Hyun Lee, In Koo Hwang, Jun Hwi Cho, Young Guen Kwon, Young Myeong Kim, Moo Ho Won

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29 Citations (Scopus)

Abstract

Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic injury by activating specific mechanisms. In this study, we tested the hypothesis that IPC attenuates postischemic neuronal death via heme oxygenase-1 (HO-1). Animals used in this study were randomly assigned to 4 groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group and IPC+ischemia-operated group. IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. A significant loss of neurons was observed in pyramidal neurons of the hippocampal CA1 region (CA1) in the ischemia-operated groups at 5 days postischemia. In the IPC+ischemia-operated groups, CA1 pyramidal neurons were well protected. The level of HO-1 protein and its activity increased significantly in the CA1 of the IPC+sham-operated group, and the level and activity was maintained in all the time after ischemia-reperfusion compared with the ischemia-operated groups. HO-1 immunoreactivity was induced in the CA1 pyramidal neurons in both IPC+sham-operated- and IPC+ischemia-operated groups. We also found that levels or immunoreactivities of superoxide anion, 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal were significantly decreased in the CA1 of both IPC+sham-operated- and IPC+ischemia-operated groups. Whereas, treatment with zinc protoporphyrin IX (a HO-1 inhibitor) into the IPC+ischemia-operated groups did not preserve the IPC-mediated increase of HO-1 and lost beneficial effects of IPC by inhibiting ischemia-induced DNA damage and lipid peroxidation. In brief, IPC protects CA1 pyramidal neurons from ischemic injury by upregulating HO-1, and we suggest that the enhancement of HO-1 expression by IPC may be a legitimate strategy for a therapeutic intervention of cerebral ischemic damage.

Original languageEnglish
Pages (from-to)78-90
Number of pages13
JournalFree Radical Biology and Medicine
Volume79
DOIs
Publication statusPublished - 2015 Feb

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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    Lee, J. C., Kim, I. H., Park, J. H., Ahn, J. H., Cho, J. H., Cho, G. S., Tae, H. J., Chen, B. H., Yan, B. C., Yoo, K. Y., Choi, J. H., Lee, C. H., Hwang, I. K., Cho, J. H., Kwon, Y. G., Kim, Y. M., & Won, M. H. (2015). Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1. Free Radical Biology and Medicine, 79, 78-90. https://doi.org/10.1016/j.freeradbiomed.2014.11.022