期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 39, 期 3, 页码 392-402出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2005.03.027
关键词
transient forebrain ischemia; reactive oxygen species; oxidative damage; Cu,Zn-superoxide dismutase; chaperone for superoxide dismutase; neuroprotection; hippocampal pyramidal cells; gerbil; free radicals
资金
- NHLBI NIH HHS [R01 HL063700, R01 HL063700-07] Funding Source: Medline
- NIEHS NIH HHS [R21 ES013986-02, R21 ES013986] Funding Source: Medline
In the present study, we investigated the chronological alterations in SOD I and its copper chaperone (chaperone for superoxide dismutase, CCS) immunoreactivities and their neuroprotective effects against neuronal damage in the gerbil hippocampus after 5 min of transient forebrain ischemia. SOD1 and CCS immunoreactivities were significantly increased in the stratum pyramidale of the CA1 region at 24 and 12 h after ischemic insult, respectively. At 24 h after ischemic insult, the SOD I and CCS immunoreactivities were colocalized in the CA1 pyramidal cells of the stratum pyramidale. Thereafter, their immunoreactivities were significantly decreased in the CA1 region. To elucidate the effects of CCS or CCS/SOD1, we constructed the expression vectors PEP-1-SOD and PEP-1-CCS. In the CCS-treated group and the CCS/SOD1-treated group, 43.9 and 78.9% pyramidal cells, respectively, compared to the sham-operated group, were stained with cresyl violet 5 or 7 days after ischemic insult. The distribution pattern of active astrocytes and microglia in the PEP-CCS/SOD1-treated group 5 days after ischemic insult was similar to that of the sham-operated group. In addition, the SOD activity in the PEP-CCS- or PEP-CCS/SOD1-treated group was maintained by 10 days after ischemic insult. The SOD activity was higher in the PEP-CCS/SOD1-treated group vs the CCS-treated group. These results suggest that the enhanced expression of SOD1 and CCS may be related to compensatory mechanisms against ischemic damage and that cotreatment with CCS and SOD I has a greater neuroprotective effect than treatment with CCS or SOD I in isolation. (c) 2005 Elsevier Inc. All rights reserved.
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