Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats.
OBJECTIVE
To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism.


METHODS
Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10-min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions.


RESULTS
Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P < 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates (P < 0.01 vs 10-min ischemia group).


CONCLUSIONS
Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.
Department of Neurosurgery, First Hospital Affiliated to Jilin University, Changchun 130021, China.
Peng-Fei
PF
Ge
Tian-Fei
TF
Luo
Ji-Zhou
JZ
Zhang
Da-Wei
DW
Chen
Yong-Xin
YX
Luan
Shuang-Lin
SL
Fu
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D016923:Cell Death; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D011506:Proteins