Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Embury, J.
Right arrow Articles by Pastori, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Embury, J.
Right arrow Articles by Pastori, R. L.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 50:1706-1713, 2001
© 2001 by the American Diabetes Association, Inc.

Proteins Linked to a Protein Transduction Domain Efficiently Transduce Pancreatic Islets

Jennifer Embury, Dagmar Klein, Antonello Pileggi, Melina Ribeiro, Sundararajan Jayaraman, R. Damaris Molano, Christopher Fraker, Norma Kenyon, Camillo Ricordi, Luca Inverardi, and Ricardo L. Pastori

Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida

The resounding success of a new immunosuppressive regimen known as the Edmonton protocol demonstrates that islet cell transplantation is becoming a therapeutic reality for diabetes. However, under the Edmonton protocol, a single donor does not provide enough islets to attain the insulin independence of a transplant recipient. This limitation is mainly caused by islet apoptosis triggered during isolation. In this study, we describe a highly efficient system of transiently transferring anti-apoptotic proteins into pancreatic islets, thus opening an exciting new therapeutic opportunity to improve the viability of transplantable islets. We fused ß-galactosidase to the 11–amino acid residues that constitute the protein transduction domain (PTD) of the HIV/TAT protein and transduced pancreatic islets ex vivo with this fusion protein in a dose-dependent manner with >80% efficiency. We observed that transduction of the anti-apoptotic proteins Bcl-XL and PEA-15 fused to TAT/PTD prevented apoptosis induced by tumor necrosis factor-{alpha} in a pancreatic ß-cell line, indicating that TAT/PTD anti-apoptotic proteins retained their biological activity. Finally, we demonstrated that TAT-fusion proteins did not affect the insulin secretion capability of islets, as determined by glucose static incubation and by reversion of hyperglycemia in diabetic immunodeficient mice.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
J. Lu, G. Li, M. S. Lan, S. Zhang, W. Fan, H. Wang, and D. Lu
Pax4 Paired Domain Mediates Direct Protein Transduction into Mammalian Cells
Endocrinology, November 1, 2007; 148(11): 5558 - 5565.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
F. Renault-Mihara, F. Beuvon, X. Iturrioz, B. Canton, S. De Bouard, N. Leonard, S. Mouhamad, A. Sharif, J. W. Ramos, M.-P. Junier, et al.
Phosphoprotein Enriched in Astrocytes-15 kDa Expression Inhibits Astrocyte Migration by a Protein Kinase C{delta}-dependent Mechanism
Mol. Biol. Cell, December 1, 2006; 17(12): 5141 - 5152.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. Krueger, F.-L. Chou, A. Glading, E. Schaefer, and M. H. Ginsberg
Phosphorylation of Phosphoprotein Enriched in Astrocytes (PEA-15) Regulates Extracellular Signal-regulated Kinase-dependent Transcription and Cell Proliferation
Mol. Biol. Cell, August 1, 2005; 16(8): 3552 - 3561.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Dominguez-Bendala, D. Klein, M. Ribeiro, C. Ricordi, L. Inverardi, R. Pastori, and H. Edlund
TAT-Mediated Neurogenin 3 Protein Transduction Stimulates Pancreatic Endocrine Differentiation In Vitro
Diabetes, March 1, 2005; 54(3): 720 - 726.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. Marchetti, M.-A. Gallego, A. Defossez, P. Formstecher, and P. Marchetti
Staining of human sperm with fluorochrome-labeled inhibitor of caspases to detect activated caspases: correlation with apoptosis and sperm parameters
Hum. Reprod., May 1, 2004; 19(5): 1127 - 1134.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Ricordi
Lilly Lecture 2002: Islet Transplantation: A Brave New World
Diabetes, July 1, 2003; 52(7): 1595 - 1603.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. K. Rehman, S. Bertera, R. Bottino, A. N. Balamurugan, J. C. Mai, Z. Mi, M. Trucco, and P. D. Robbins
Protection of Islets by in Situ Peptide-mediated Transduction of the Ikappa B Kinase Inhibitor Nemo-binding Domain Peptide
J. Biol. Chem., March 7, 2003; 278(11): 9862 - 9868.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Asoh, I. Ohsawa, T. Mori, K.-i. Katsura, T. Hiraide, Y. Katayama, M. Kimura, D. Ozaki, K. Yamagata, and S. Ohta
Protection against ischemic brain injury by protein therapeutics
PNAS, December 24, 2002; 99(26): 17107 - 17112.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Ohara-Imaizumi, Y. Nakamichi, C. Nishiwaki, and S. Nagamatsu
Transduction of MIN6 beta Cells with TAT-Syntaxin SNARE Motif Inhibits Insulin Exocytosis in Biphasic Insulin Release in a Distinct Mechanism Analyzed by Evanescent Wave Microscopy
J. Biol. Chem., December 20, 2002; 277(52): 50805 - 50811.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2001 by the American Diabetes Association.