View in EDS

Efficient delivery of siRNA into cytokine-stimulated insulinoma cells silences Fas expression and inhibits Fas-mediated apoptosis

Saved in:
Bibliographic Details
Title: Efficient delivery of siRNA into cytokine-stimulated insulinoma cells silences Fas expression and inhibits Fas-mediated apoptosis
Authors: Burkhardt, Brant R.1, Lyle, Rachel2, Qian, Keping2, Arnold, Anne-Sophie2, Cheng, Henrique2, Atkinson, Mark A.3, Zhang, Y. Clare2 czhang@hsc.usf.edu
Source: FEBS Letters. Jan2006, Vol. 580 Issue 2, p553-560. 8p.
Subjects: RNA, Cytokines, Islands of Langerhans tumors, Apoptosis
Abstract: Abstract: Fas/FasL interactions have been proposed as a potentially important mechanism mediating β-cell death in type 1 diabetes. Recent investigations suggest RNA interference, afforded by small interfering RNAs (siRNA), can provide specific and robust gene silencing in mammalian cells. The current study attempted to investigate the effects of silencing Fas expression with siRNA on Fas-mediated apoptosis in mouse insulinoma cells following cytokine incubation. Our results indicate that siRNA is capable of rapid inhibition of cytokine-induced Fas mRNA production and cell surface Fas protein. A complete suppression of the total Fas protein was only observed after prolonged incubation with siRNA, suggesting a slow turn-over of Fas protein. Moreover, siRNA significantly inhibited Fas-mediated β-cell apoptosis assessed by Caspase-3 and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assays, the extent of which positively correlated with the level of cell surface Fas. These observations provide additional evidence supporting a role for the Fas-mediated pathway in β-cell destruction, and suggest that siRNA targeting Fas may be of therapeutic value in preventing type 1 diabetes and improving islet cell viability in transplantation. [Copyright &y& Elsevier]
Copyright of FEBS Letters is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
Description
Abstract:Abstract: Fas/FasL interactions have been proposed as a potentially important mechanism mediating β-cell death in type 1 diabetes. Recent investigations suggest RNA interference, afforded by small interfering RNAs (siRNA), can provide specific and robust gene silencing in mammalian cells. The current study attempted to investigate the effects of silencing Fas expression with siRNA on Fas-mediated apoptosis in mouse insulinoma cells following cytokine incubation. Our results indicate that siRNA is capable of rapid inhibition of cytokine-induced Fas mRNA production and cell surface Fas protein. A complete suppression of the total Fas protein was only observed after prolonged incubation with siRNA, suggesting a slow turn-over of Fas protein. Moreover, siRNA significantly inhibited Fas-mediated β-cell apoptosis assessed by Caspase-3 and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assays, the extent of which positively correlated with the level of cell surface Fas. These observations provide additional evidence supporting a role for the Fas-mediated pathway in β-cell destruction, and suggest that siRNA targeting Fas may be of therapeutic value in preventing type 1 diabetes and improving islet cell viability in transplantation. [Copyright &y& Elsevier]
ISSN:00145793
DOI:10.1016/j.febslet.2005.12.068