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

Cell Death Differ. 2000 Mar;7(3):314-26. doi: 10.1038/sj.cdd.4400658.

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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Carrier Proteins / metabolism
  • Cell Division / drug effects
  • Deoxycholic Acid / pharmacology*
  • Detergents / pharmacology
  • Enzyme Precursors
  • Glutathione / metabolism
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • HT29 Cells
  • Heat-Shock Proteins*
  • Humans
  • Jurkat Cells
  • Molecular Chaperones / metabolism
  • NAD / metabolism*
  • NF-kappa B / metabolism
  • Niacin / metabolism
  • Niacin / pharmacology*
  • Niacinamide / metabolism
  • Niacinamide / pharmacology*
  • Oxidative Stress

Substances

  • Carrier Proteins
  • Detergents
  • Enzyme Precursors
  • Heat-Shock Proteins
  • Molecular Chaperones
  • NF-kappa B
  • Deoxycholic Acid
  • NAD
  • Niacinamide
  • Niacin
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Glutathione
  • molecular chaperone GRP78