Ischemic preconditioning prevents protein aggregation after transient cerebral ischemia.
Transient cerebral ischemia leads to protein aggregation mainly in neurons destined to undergo delayed neuronal death after ischemia. This study utilized a rat transient cerebral ischemia model to investigate whether ischemic preconditioning is able to alleviate neuronal protein aggregation, thereby protecting neurons from ischemic neuronal damage. Ischemic preconditioning was introduced by a sublethal 3 min period of ischemia followed by 48 h of recovery. Brains from rats with either ischemic preconditioning or sham-surgery were then subjected to a subsequent 7 min period of ischemia followed by 30 min, 4, 24, 48 and 72 h of reperfusion. Protein aggregation and neuronal death were studied by electron and confocal microscopy, as well as by biochemical analyses. Seven minutes of cerebral ischemia alone induced severe protein aggregation after 4 h of reperfusion mainly in CA1 neurons destined to undergo delayed neuronal death (which took place after 72 h of reperfusion). Ischemic preconditioning reduced significantly protein aggregation and virtually eliminated neuronal death in CA1 neurons. Biochemical analyses revealed that ischemic preconditioning decreased accumulation of ubiquitin-conjugated proteins (ubi-proteins) and reduced free ubiquitin depletion after brain ischemia. Furthermore, ischemic preconditioning also reduced redistribution of heat shock cognate protein 70 and Hdj1 from cytosolic fraction to protein aggregate-containing fraction after brain ischemia. These results suggest that ischemic preconditioning decreases protein aggregation after brain ischemia.
Liu
C
C
Department of Neurology, University of Miami School of Medicine, PO Box 16960, Miami, FL 33136, USA.
Chen
S
S
Kamme
F
F
Hu
B R
BR
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D011419:Propidium; D011506:Proteins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism
C494643:Dnaja2 protein, rat; D050956:HSP40 Heat-Shock Proteins; D011506:Proteins; D025801:Ubiquitin; D011419:Propidium