alexa An oxidative mechanism of interferon induced priming of the Fas pathway in Fanconi anemia cells.
Reproductive Medicine

Reproductive Medicine

Reproductive System & Sexual Disorders: Current Research

Author(s): PearlYafe M, Halperin D, Halevy A, Kalir H, Bielorai B,

Abstract Share this page

Abstract Hematopoietic progenitor cells from children with Fanconi anemia of the C complementation group (FA-C) are excessively apoptotic and hypersensitive to various extracellular cues including Fas-ligand, tumor necrosis factor-alpha and double-stranded RNA. Interferon (IFN)-gamma is known to augment apoptotic responses of these factors. The "priming" effect of IFN-gamma is not fully explained. In view of the strong evidence that FA cells are intolerant of oxidative stress, we tested the notion that IFN-priming involves the induction of reactive oxygen species (ROS) in two FA-C B-lymphocyte cell lines and in peripheral blood neutrophils and mononuclear cells of FA patients. We also investigated whether the combination of IFN-gamma and Fas created an intracellular environment that promoted apoptosis. Significantly lower doses of IFN-gamma induced ROS accumulation in neutrophils and mononuclear cell of FA patients compared to cells of normal individuals. Enhanced ROS accumulation and decreased intracellular glutathione levels were observed in FA-C B-cell lines primed with IFN-gamma and treated with agonistic anti-Fas antibody than in isogenic control cells corrected with FANCC. The above treatment also induced caspase-3 and -8 activation as well as apoptosis. That antioxidants reduced the priming effect of IFN-gamma in Fas and IFN-gamma-treated FA lymphoblast cells, demonstrates that ROS represent a critical effector mechanism for the exaggerated responses to IFN-gamma characteristic of FA-C cells.
This article was published in Biochem Pharmacol and referenced in Reproductive System & Sexual Disorders: Current Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • International Meeting on Women's Health and Breast Cancer
    Oct 12, 2017, Dubai, UAE
  • International Conference on Gynecology and Obstetrics Pathology
    October 23-24, 2017 Orlando, USA
  • 5th International Conference on HIV/AIDS, STDs and STIs
    Nov 13-14, 2017, Las Vegas, Nevada, USA

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version