Tell us what you do - Claudia Benavente, Ph.D.
Claudia Benavente
Thursday, 23 October 2008 17:42 UTC
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Claudia Benavente, Ph.D.
Regional Director USA
c.benavente@bionexa.org
www.bionexa.org
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Replies
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NAD+ is a substrate for many enzymes, including poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs), which are involved in fundamental cellular processes including DNA repair, stress responses, signaling, transcription, apoptosis, metabolism, differentiation, chromatin structure, and life span. Because these molecular processes are important early in cancer development, we developed a model to identify critical NAD-dependent pathways potentially important in early skin carcinogenesis. Removal of niacin from the cell culture medium allowed control of intracellular NAD. Unlike many non-immortalized human cells, HaCaT keratinocytes, which are immortalized and have a mutant p53 and aberrant NF-kB activity, become severely NAD depleted but divide indefinitely under these conditions. Niacin deficient HaCaTs develop a decreased growth rate due to an increase in apoptotic cells and an arrest in the G2/M phase of the cell cycle. Long- term survival mechanisms in niacin deficient HaCaTs involve accumulation of reactive oxygen species (ROS) and increased DNA damage. These alterations result, at least in part, from increased expression and activity of NADPH oxidase, whose downstream effects can be reversed by nicotinamide or NADPH oxidase inhibitors. Our data support the hypothesis that glutamine is a likely alternative energy source during niacin deficiency and we have suggested a model for NADPH generation important in ROS production.
Benavente CA, Jacobson EL, Niacin restriction upregulates NADPH oxidase and ROS in human keratinocytes. Free Radical Biology and Medicine. 2008 Feb 15; 44(4):527-37. Epub 2007 Oct 17.
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Question:
Do you think small molecules/vitamins can be used in the prevention on diseases like cancer? What are the risks? What cautionary measures should we take?
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