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NUCLEAR FACTOR κB BINDING ACTIVITY IN MOUSE L1210 CELLS FOLLOWING PHOTOFRIN II-MEDIATED PHOTOSENSITIZATION
Authors:Stefan W  Ryter Charles J  Gomer
Institution:Department of Molecular Pharmacology, Radiation Oncology, University of Southern California;Department of Pediatrics, University of Southern California;Department of Radiation Oncology, University of Southern California;Clayton Ocular Oncology Center, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
Abstract:Clinical photodynamic therapy (PDT) uses the photosensitizer photofnn II to produce singlet molecular oxygen and other reactive oxygen intermediates for localized tumor tissue cytotoxicity. In this report, we show that PDT enhances the DNA binding activity of nuclear factor kappa B (NFkB), a transacti vator of cytokine gene expression. Photosensitization following a 16 h incubation of photofrin II induced NFkB binding activity in mouse leukemia L1210 cells 10-fold above that observed in exponentially growing cultures. Serum starvation, as well as drug-alone and light-alone controls, elevated basal NF k B binding activity two- to three-fold. Upstream stimulatory factor binding activity was not modulated by any of the cell treatments and was used to standardize gel mobility shift data. This study identifies porphynn-mediated PDT as an inducer of NF k B binding activity, extending recent findings that NF k B activation is a general response to oxidative stress.
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