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

Publication ,  Journal Article
Contreras, JL; Smyth, CA; Bilbao, G; Eckstein, C; Young, CJ; Thompson, JA; Curiel, DT; Eckhoff, DE
Published in: Transpl Int
July 2003

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.

Duke Scholars

Published In

Transpl Int

DOI

ISSN

0934-0874

Publication Date

July 2003

Volume

16

Issue

7

Start / End Page

537 / 542

Location

Switzerland

Related Subject Headings

  • Tunicamycin
  • Surgery
  • Proto-Oncogene Proteins c-bcl-2
  • Islets of Langerhans
  • Inflammation Mediators
  • Humans
  • Genes, bcl-2
  • Gene Transfer Techniques
  • Enzyme Activation
  • Endoplasmic Reticulum
 

Citation

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Contreras, J. L., Smyth, C. A., Bilbao, G., Eckstein, C., Young, C. J., Thompson, J. A., … Eckhoff, D. E. (2003). Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2. Transpl Int, 16(7), 537–542. https://doi.org/10.1007/s00147-003-0619-x
Contreras, Juan L., Cheryl A. Smyth, Guadalupe Bilbao, Christopher Eckstein, Carlton J. Young, J Anthony Thompson, David T. Curiel, and Devin E. Eckhoff. “Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2.Transpl Int 16, no. 7 (July 2003): 537–42. https://doi.org/10.1007/s00147-003-0619-x.
Contreras JL, Smyth CA, Bilbao G, Eckstein C, Young CJ, Thompson JA, et al. Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2. Transpl Int. 2003 Jul;16(7):537–42.
Contreras, Juan L., et al. “Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2.Transpl Int, vol. 16, no. 7, July 2003, pp. 537–42. Pubmed, doi:10.1007/s00147-003-0619-x.
Contreras JL, Smyth CA, Bilbao G, Eckstein C, Young CJ, Thompson JA, Curiel DT, Eckhoff DE. Coupling endoplasmic reticulum stress to cell death program in isolated human pancreatic islets: effects of gene transfer of Bcl-2. Transpl Int. 2003 Jul;16(7):537–542.
Journal cover image

Published In

Transpl Int

DOI

ISSN

0934-0874

Publication Date

July 2003

Volume

16

Issue

7

Start / End Page

537 / 542

Location

Switzerland

Related Subject Headings

  • Tunicamycin
  • Surgery
  • Proto-Oncogene Proteins c-bcl-2
  • Islets of Langerhans
  • Inflammation Mediators
  • Humans
  • Genes, bcl-2
  • Gene Transfer Techniques
  • Enzyme Activation
  • Endoplasmic Reticulum