Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic β-cells

Melina M. Ribeiro, Dagmar Klein, Antonello Pileggi, R. Damaris Molano, Christopher Fraker, Camillo Ricordi, Luca Inverardi, Ricardo L. Pastori

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Transplantation of islets is becoming an established method for treating type 1 diabetes. However, viability of islets is greatly affected by necrosis/apoptosis induced by oxidative stress and other insults during isolation and subsequent in vitro culture. Expression of cytoprotective proteins, such as heme oxygenase-1 (HO-1), reduces the deleterious effects of oxidative stress in transplantable islets. We have generated a fusion protein composed of HO-1 and TAT protein transduction domain (TAT/PTD), an 11-aa cell penetrating peptide from the human immunodeficiency virus TAT protein. Transduction of TAT/PTD-HO-1 to insulin-producing cells protects against TNF-α-mediated cytotoxicity. TAT/PTD-HO-1 transduction to islets does not impair islet physiology, as assessed by reversion of chemically induced diabetes in immunodeficient mice. Finally, we report that transduction of HO-1 fusion protein into islets improves islet viability in culture. This approach might have a positive impact on the availability of islets for transplantation.

Original languageEnglish (US)
Pages (from-to)876-881
Number of pages6
JournalBiochemical and biophysical research communications
Volume305
Issue number4
DOIs
StatePublished - Jun 13 2003

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Keywords

  • Heme oxygenase-1
  • Islets
  • Pancreatic β-cells
  • Protein transduction domain
  • TAT

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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