Background: HS is an endogenous gas signal molecule, which protects cerebral ischemia/reperfusion (I/R) injury by phosphorylating rho-associated coiled coil-containing protein kinase 2 (ROCK) at Tyr722, and inhibiting ROCK protein expression and activities. We previously reported that HS protected rat neurons from hypoxia/reoxygenation injury in vitro through inhibiting phosphorylation of ROCK at Thr436 and Ser575, but it is unclear whether these two sites are involved in protection of HS against cerebral I/R injury.
Method: Rats transfected with wild-type and mutant eukaryotic plasmids of ROCK in hippocampus were used to establish I/R model by ligating bilateral common carotid artery. Rat behavioral deficit was detected by water maze assay, and ROCK, lactate dehydrogenase (LDH), nerve-specific enolase (NSE) and reactive oxygen species (ROS) were determined by ELISA. ROCK expressions was examined by western-blot assay, and bcl-2 and Bax mRNAs were examined by RT-qPCR.
Results: NaHS (4.8 mg/kg) significantly inhibited the I/R-increased serum LDH, NSE and ROS in the ROCK-pEGFP-N1-transfected rats, but had no obvious effect in the ROCK-pEGFP-N1- or the ROCK-pEGFP-N1-transfected rats; inhibitions of NaHS on the I/R-increased escape latency and the I/R-decreased percentage of target quadrant distance to total distance were markedly attenuated or abolished in the ROCK-pEGFP-N1- or the ROCK-pEGFP-N1-transfected rats compared with those in the ROCK-pEGFP-N1-transfected rats; NaHS obviously inhibited the I/R-increased hippocampal ROCK and GFP-ROCK proteins, Bax mRNA, and ROCK activity, as well as the I/R-decreased hippocampal bcl-2 mRNA in the hippocampus of the ROCK-pEGFP-N1-transfected rats, but had no significant effect in the ROCK-pEGFP-N1- or the ROCK-pEGFP-N1-transfected rats.
Conclusion: HS protects cerebral I/R injury in rats by inhibiting expression and activation of hippocampal ROCK via the Thr436 and Ser575 sites.
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