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

Juan L. Contreras, Cheryl A. Smyth, Guadalupe Bilbao, Christopher Eckstein, Carlton J. Young, J. Anthony Thompson, David T. Curiel, Devin E. Eckhoff

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

A variety of toxic insults can result in endoplasmic reticulum (ER)-stress that ultimately leads to apoptosis. β-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.

Original languageEnglish
Pages (from-to)537-542
Number of pages6
JournalTransplant International
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2003

Keywords

  • Apoptosis
  • Bcl-2
  • Endoplasmic reticulum
  • Islet transplantation

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