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Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic beta-cells
- Source :
- Biochemical and biophysical research communications. 305(4)
- Publication Year :
- 2003
-
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-alpha-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.
- Subjects :
- endocrine system
endocrine system diseases
Cell Survival
Recombinant Fusion Proteins
Biophysics
Cell Culture Techniques
Islets of Langerhans Transplantation
Biology
Biochemistry
Cell Line
Transduction (genetics)
Islets of Langerhans
Insulin Secretion
Animals
Insulin
Amino Acid Sequence
Molecular Biology
Cells, Cultured
geography
geography.geographical_feature_category
Cell Biology
Islet
Fusion protein
Transport protein
Cell biology
Protein Structure, Tertiary
Rats
Transplantation
Heme oxygenase
Protein Transport
Cell culture
Apoptosis
Cytoprotection
Rats, Inbred Lew
Gene Products, tat
Heme Oxygenase (Decyclizing)
Peptides
Heme Oxygenase-1
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 305
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....b59f2f52a5a8f264f1d47ed34df8a0ed