Abstract
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.
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Acknowledgments
Dr. Ogawa is an Alexander von Humboldt fellow and the current studies were partially financed by the Alexander von Humboldt Foundation.
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We declare that we have no conflict of interest.
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Ogawa, T., Hänggi, D., Steiger, HJ. (2011). Treatment of Experimental Cerebral Vasospasm by Protein Transduction of Heme Oxygenase 1 (HO-1) Conjugated to a Residue of 11 Arginines. In: Tsukahara, T., Regli, L., Hänggi, D., Turowski, B., Steiger, HJ. (eds) Trends in Neurovascular Surgery. Acta Neurochirurgica Supplementum, vol 112. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0661-7_20
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