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

Ribeiro, MM, Klein, D, Pileggi, A et al. (2003). Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic β-cells . BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 305(4), 876-881. 10.1016/S0006-291X(03)00856-8

cited authors

  • Ribeiro, MM; Klein, D; Pileggi, A; Molano, RD; Fraker, C; Ricordi, C; Inverardi, L; Pastori, RL

authors

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. © 2003 Elsevier Science (USA). All rights reserved.

publication date

  • June 13, 2003

published in

Digital Object Identifier (DOI)

start page

  • 876

end page

  • 881

volume

  • 305

issue

  • 4