Delivery of Bcl-XL or its BH4 domain by protein transduction inhibits apoptosis in human islets Article

Klein, D, Ribeiro, MM, Mendoza, V et al. (2004). Delivery of Bcl-XL or its BH4 domain by protein transduction inhibits apoptosis in human islets . BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 323(2), 473-478. 10.1016/j.bbrc.2004.08.116

cited authors

  • Klein, D; Ribeiro, MM; Mendoza, V; Jayaraman, S; Kenyon, NS; Pileggi, A; Molano, RD; Inverardi, L; Ricordi, C; Pastori, RL

authors

abstract

  • Viability of isolated islets is one of the main obstacles limiting islet transplantation success. It has been reported that overexpression of Bcl-2/Bcl-XL proteins enhances islet viability. To avoid potential complications associated with long-term expression of anti-apoptotic proteins, we investigated the possibility of delivering Bcl-XL or its anti-apoptotic domain BH4 to islets by protein transduction. Bcl-XL and BH4 molecules were fused to TAT/PTD, the 11-aa cell penetrating peptide from HIV-1 transactivating protein, generating TAT-Bcl-XL and TAT-BH4, respectively. Transduction efficiency was assessed by laser scanning confocal microscopy of live islets. Biological activity was tested as the ability to protect NIT-1 insulinoma cell line from death induced by staurosporine or serum deprivation. Spontaneous caspase activation in human islets and cytotoxicity caused by IL-1β were significantly reduced in the presence of TAT-Bcl-XL and TAT-BH4. We conclude that both TAT proteins are biologically active after transduction and could be an asset in the improvement of islet viability. © 2004 Elsevier Inc. All rights reserved.

publication date

  • October 15, 2004

published in

Digital Object Identifier (DOI)

start page

  • 473

end page

  • 478

volume

  • 323

issue

  • 2