The NAD(+) precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate

The bile salt, sodium deoxycholate (NaDOC), is a natural detergent that pro motes digestion of fats. At high physiologic levels, NaDOC activates many s tress-response pathways and induces apoptosis in various cell types. NaDOC induces DNA damage and activates poly(ADP-ribose) polymerase (PARP), an enz yme that utilizes NAD(+) as a substrate to repair DNA. NaDOC also induces o xidative stress, endoplasmic reticulum (ER) stress and contributes to prote in malfolding. The NAD(+) precursors, nicotinic acid (NA) and nicotinamide (NAM) were found to protect cells against NaDOC-induced apoptosis. NA and N AM also decreased constitutive levels of both activated NF-kappa B and GRP7 8, two proteins that respond to oxidative stress. However, the mechanism by which NA and NAM protects cells against apoptosis does not involve a reduc tion in constitutive levels of oxidative stress. NA or NAM treatment increa sed the protein levels of glyceraldehyde-3-phosphate dehydrogense (GAPDH), a multi-functional enzyme, in the nucleus and cytoplasm, respectively. NAM did not activate the promoter/response elements of 13 stress response genes nor reduce intracellular non-protein thiols, suggesting that if is non-tox ic to cells, NAM thus has promise as a dietary supplement to help prevent d isorders involving excessive apoptosis.