Treatment of experimental cerebral vasospasm by protein transduction of heme oxygenase 1 (HO-1) conjugated to a residue of 11 arginines.

BACKGROUND: Many kinds of proteins can be transduced into various cells by conjugation with 10-20 amino acid peptides. A sequence of 11 consecutive arginine groups (11R) is one of the most efficient protein transduction domains (PTD). We used the 32-kDa heat shock protein heme oxygenase-1 (HO-1) as a therapeutic protein for experimental cerebral vasospasm. This protein is an enzyme of the heme-catabolism and cleaves heme to form biliverdin and carbon monoxide (CO). HO-1 has known vascular relaxing properties. We examined the transduction efficacy and antispastic therapeutic effect of 11R fused HO-1 protein in cerebral arteries.

METHODS: 11R fused HO-1 protein was expressed purified. An MTT assay was used to evaluate the cytotoxicity of 11R-HO-1. An antispastic effect was investigated in a rat model of experimental subarachnoid hemorrhage by measuring basilar artery diameters 4 h after the injection of 11R-HO-1 into the cisterna.

FINDINGS: Expression and purification of 11R-HO-1 could be successfully effected. Transduction into the basilar artery was also successful. 11R-HO-1 protein has the positive effect of attenuating cerebral vasospasm.

CONCLUSION: These results suggest that the 11R-HO-1 protein transduction method has a potential to treat cerebral vasospasm.