Paradoxical effect of diphenyleneiodonium in inducing DNA damage and apoptosis.
Diphenyleneiodonium (DPI) is often used as a molecular tool in unravelling redox-sensitive cellular events involving NADPH oxidase. However, to better understand unexpected actions of DPI, it was ascertained if DPI affects cellular DNA. DPI induced single-strand breaks in DNA of HCT-116 cells, although this only slightly increased GADD153 expression. Nevertheless, after sustaining DNA damage, the DPI-treated cells subsequently had features characteristic of apoptosis, such as translocated membrane phospholipid and nuclei containing condensed chromatin. Paradoxically, DPI attenuated the DNA damage and overall ROS production caused by sodium deoxycholate (DOC), although DPI did not inhibit DOC-induced generation of mitochondrial [image omitted] . Furthermore, DPI prevented the occurrence of apoptosis caused by DOC. However, other known chemical inhibitors of NADPH oxidase did not produce the same results as DPI in negating the effects of DOC. Collectively, these disparate findings suggest that DPI can act not in accord with conventional wisdom depending on the experimental conditions.
Cellular and Molecular Nutrition Research Laboratory, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
Jennifer M
JM
Longpre
George
G
Loo
D017304:Annexin A5 / Q000737:chemistry; D017209:Apoptosis; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D020552:Comet Assay; D004249:DNA Damage; D003840:Deoxycholic Acid / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP / Q000378:metabolism*
D017304:Annexin A5; D002843:Chromatin; C497249:DDIT3 protein, human; D004791:Enzyme Inhibitors; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D003840:Deoxycholic Acid; D051742:Transcription Factor CHOP; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases