Copper chaperone for Cu,Zn-SOD supplement potentiates the Cu,Zn-SOD function of neuroprotective effects against ischemic neuronal damage in the gerbil hippocampus.
In the present study, we investigated the chronological alterations in SOD1 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 SOD1 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 SOD1 has a greater neuroprotective effect than treatment with CCS or SOD1 in isolation.
Department of Anatomy, College of Medicine, Hallym University, Chunchon 200-702, South Korea.
In Koo
IK
Hwang
Won Sik
WS
Eum
Ki-Yeon
KY
Yoo
Jun Hwi
JH
Cho
Dae Won
DW
Kim
Soo Hyun
SH
Choi
Tae-Cheon
TC
Kang
Oh-Shin
OS
Kwon
Jung Hoon
JH
Kang
Soo Young
SY
Choi
Moo Ho
MH
Won
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018832:Molecular Chaperones / Q000378:metabolism*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase / Q000378:metabolism*
D018832:Molecular Chaperones; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase