Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2.
Journal Article (Journal Article)
A variety of toxic insults can result in endoplasmic reticulum (ER)-stress that ultimately leads to apoptosis. beta-cells have a highly developed ER due to a great commitment to insulin production. The present study was carried out to determine the role of ER-stress in isolated human pancreatic islet apoptosis, and the potential protective effects of Bcl-2. Isolated human islets were infected with an adenoviral vector encoding Bcl-2 and then exposed to brefeldin-A, tunicamycin, A23187 and pro-inflammatory cytokines. Activation of caspase-12 was analyzed by means of Western blots. Apoptosis was evaluated using a commercial quantitative assay. ER-stress-inducers promoted caspase-12 activation and apoptosis, effect reversed by overexpression of Bcl-2. Co-localization of caspase-12 and Bcl-2 in the microsomal islet fractions were demonstrated by means of Western blots. We can conclude that the current studies highlight the importance of Bcl-2 as an anti-apoptotic protein, and shed new light on the mechanisms underlying its cytoprotective effects on pancreatic islets.
Full Text
Duke Authors
Cited Authors
- Contreras, JL; Smyth, CA; Bilbao, G; Eckstein, C; Young, CJ; Thompson, JA; Curiel, DT; Eckhoff, DE
Published Date
- July 2003
Published In
Volume / Issue
- 16 / 7
Start / End Page
- 537 - 542
PubMed ID
- 12819863
International Standard Serial Number (ISSN)
- 0934-0874
Digital Object Identifier (DOI)
- 10.1007/s00147-003-0619-x
Language
- eng
Conference Location
- Switzerland