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

CL Crowley, CM Payne, H Bernstein… - Cell death & …, 2000 - nature.com
CL Crowley, CM Payne, H Bernstein, C Bernstein, D Roe
Cell death & differentiation, 2000nature.com
The bile salt, sodium deoxycholate (NaDOC), is a natural detergent that promotes digestion
of fats. At high physiologic levels, NaDOC activates many stress-response pathways and
induces apoptosis in various cell types. NaDOC induces DNA damage and activates poly
(ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD+ as a substrate to repair
DNA. NaDOC also induces oxidative stress, endoplasmic reticulum (ER) stress and
contributes to protein malfolding. The NAD+ precursors, nicotinic acid (NA) and nicotinamide …
Abstract
The bile salt, sodium deoxycholate (NaDOC), is a natural detergent that promotes digestion of fats. At high physiologic levels, NaDOC activates many stress-response pathways and induces apoptosis in various cell types. NaDOC induces DNA damage and activates poly (ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD+ as a substrate to repair DNA. NaDOC also induces oxidative stress, endoplasmic reticulum (ER) stress and contributes to protein malfolding. The NAD+ precursors, nicotinic acid (NA) and nicotinamide (NAM) were found to protect cells against NaDOC-induced apoptosis. NA and NAM also decreased constitutive levels of both activated NF-κB and GRP78, two proteins that respond to oxidative stress. However, the mechanism by which NA and NAM protects cells against apoptosis does not involve a reduction in constitutive levels of oxidative stress. NA or NAM treatment increased 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 it is non-toxic to cells. NAM thus has promise as a dietary supplement to help prevent disorders involving excessive apoptosis.
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