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    
Abstract/OtherAbstract:
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.
Authors:
Dagmar Klein; Melina M Ribeiro; Valeska Mendoza; Sundararajan Jayaraman; Norma S Kenyon; Antonello Pileggi; R Damaris Molano; Luca Inverardi; Camillo Ricordi; Ricardo L Pastori
Related Documents :
17057225 - A novel role for proline- and acid-rich basic region leucine zipper (par bzip) proteins...
18790835 - Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemi...
9453635 - Identification of a putative precursor to the major surface glycoprotein of pneumocysti...
15741345 - Bcl-xl as a fusion protein for the high-level expression of membrane-associated proteins.
15752985 - Iron-sulfur-protein biogenesis in eukaryotes.
21945855 - Thiol redox requirements and substrate specificities of recombinant cytochrome c assemb...
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.
Affiliation:
Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology*
Cells, Cultured
Feasibility Studies
Genetic Enhancement / methods
Humans
Islets of Langerhans / cytology*,  drug effects,  physiology*
Primates
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
ID/Acronym/Agency:
5U42RR016603/RR/NCRR NIH HHS; DK-59993/DK/NIDDK NIH HHS
Chemical
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Microarray TRAP--a high-throughput assay to quantitate telomerase activity.
Next Document:  mPer2 antisense oligonucleotides inhibit mPER2 expression but not circadian rhythms of physiological...