Document Detail

Delivery of Bcl-XL or its BH4 domain by protein transduction inhibits apoptosis in human islets.
MedLine Citation:
PMID:  15369775     Owner:  NLM     Status:  MEDLINE    
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-1beta 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.
Dagmar Klein; Melina M Ribeiro; Valeska Mendoza; Sundararajan Jayaraman; Norma S Kenyon; Antonello Pileggi; R Damaris Molano; Luca Inverardi; Camillo Ricordi; Ricardo L Pastori
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  323     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-16     Completed Date:  2004-11-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  473-8     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Elsevier Inc.
Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA.
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MeSH Terms
Apoptosis / drug effects,  physiology*
Cells, Cultured
Feasibility Studies
Genetic Enhancement / methods
Islets of Langerhans / cytology*,  drug effects,  physiology*
Protein Engineering / methods*
Protein Structure, Tertiary / genetics
Proto-Oncogene Proteins c-bcl-2 / genetics*,  metabolism*
Recombinant Proteins / metabolism
Staurosporine / pharmacology
Transduction, Genetic / methods*
bcl-X Protein
Grant Support
Reg. No./Substance:
0/BCL2L1 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Recombinant Proteins; 0/bcl-X Protein; 62996-74-1/Staurosporine

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