Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2.

Published

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

Pubmed Central ID

  • 12819863

International Standard Serial Number (ISSN)

  • 0934-0874

Digital Object Identifier (DOI)

  • 10.1007/s00147-003-0619-x

Language

  • eng

Conference Location

  • England