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

被引:95
作者
Crowley, CL
Payne, CM [1 ]
Bernstein, H
Bernstein, C
Roe, D
机构
[1] Univ Arizona, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA
[2] Univ Arizona, Arizona Canc Ctr, Div Biometry, Tucson, AZ 85724 USA
关键词
nicotinic acid; nicotinamide; NAD; NF-kappa B; GRP78; PARP;
D O I
10.1038/sj.cdd.4400658
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-kappa B 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 if is non-toxic to cells, NAM thus has promise as a dietary supplement to help prevent disorders involving excessive apoptosis.
引用
收藏
页码:314 / 326
页数:13
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