Protein therapy using heme-oxygenase-1 fused to a polyarginine transduction domain attenuates cerebral vasospasm after experimental subarachnoid hemorrhage

Tomoyuki Ogawa, Daniel Hänggi, Yumei Wu, Hiroyuki Michiue, Kazuhito Tomizawa, Shigeki Ono, Hideki Matsui, Isao Date, Hans Jakob Steiger

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A sequence of 11 consecutive arginine residues (11R) is one of the best protein transduction domains for introducing proteins into cell membranes. Heme-oxygenase-1 (HO-1) is involved in heme catabolism and reduces the contractile effect of hemoglobin after subarachnoid hemorrhage (SAH). Therefore, we constructed 11R-fused HO-1 protein to achieve successful transduction of the protein into the cerebral arteries and examined the therapeutic effect of the 11R-HO-1 protein for cerebral vasospasm (CV) after SAH. We injected the 11R-HO-1 protein into the cisterna magna of male rats and, several hours after the injection, performed immunofluorescence staining and western blotting analysis of the rat basilar arteries (BAs) to determine transduction efficacy. We also assessed intraarterial HO-1 activity as cGMP (cyclic guanosine 3′, 5′-cyclic monophosphate) accumulation in SAH and determined whether protein transduction of 11R-HO-1 quantified the therapeutic effect in a rat double-hemorrhage model of SAH. The BAs expressed significantly more HO-1 in the group injected with 11R-HO-1 (3.560.54 (11R-HO-1) versus control (saline)), and transduction of 11R-HO-1 resulted in higher activity (3.25-fold) in rat BAs with SAH. Moreover, the results of the rat double-hemorrhage model showed that the 11R-HO-1 protein significantly attenuated CV after SAH (317.5923.48 m (11R-HO-1) versus 270.0814.66 m (11R-fused enhanced green fluorescent protein), 252.0513.95 m (saline), P0.01).

Original languageEnglish
Pages (from-to)2231-2242
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • 11 consecutive arginines (11R)
  • cerebral vasospasm
  • heme-oxygenase-1 (HO-1)
  • protein transduction domain (PTD)
  • subarachnoid hemorrhage (SAH)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Protein therapy using heme-oxygenase-1 fused to a polyarginine transduction domain attenuates cerebral vasospasm after experimental subarachnoid hemorrhage'. Together they form a unique fingerprint.

  • Cite this