Open AccessCoupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl‐2
Author(s) -
Contreras Juan L.,
Smyth Cheryl A.,
Bilbao Guadalupe,
Eckstein Christopher,
Young Carlton J.,
Thompson J. Anthony,
Curiel David T.,
Eckhoff Devin E.
Publication year - 2003
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2003.tb00344.x
Subject(s) - endoplasmic reticulum , unfolded protein response , apoptosis , tunicamycin , microbiology and biotechnology , pancreatic islets , islet , thapsigargin , blot , programmed cell death , brefeldin a , medicine , endocrinology , biology , insulin , gene , biochemistry , golgi apparatus
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.