Nicotinamide as a precursor for NAD+ prevents apoptosis in the mouse brain induced by tertiary-butylhydroperoxide

Klaidman, Lori K.; Mukherjee, Suman; Hutchin, Tim; Adams, James D.

doi:10.1016/0304-3940(96)12446-0

Cited by 85 publications

(50 citation statements)

References 16 publications

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“…This could be explained by the fact that NAM is a weak PARP inhibitor, whereas NA has no effect on PARP activity. 88 A protective effect of NAM against apoptosis was also demonstrated in the in vivo studies of Klaidman et al 89 and Mukherjee et al, 90 who showed that NAM treatment prevented neuronal apoptosis produced by tertiary-butylhydroperoxide, 89 an organic peroxide, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 90 a neurotoxin. A major finding of the present study was that both NA and NAM decreased NF-kB, as measured by a decrease in the activated form of NF-kB and a decrease in protein expression of the NF-kB(p50) and NF-kB(p65) proteins.…”

Section: Discussionmentioning

confidence: 78%

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

et al. 2000

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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-kB 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. Cell Death and Differentiation (2000) 7, 314 ± 326.

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Section: Discussionmentioning

confidence: 78%

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

et al. 2000

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“…5,6 Via its major metabolite, NAD (nicotinamide adenine dinucleotide), NA is also involved in a wide range of biological processes: production of energy, synthesis of fatty acids, cholesterol and steroids, signal transduction and maintenance of the integrity of the genome. [7][8][9] PA was found to be a strong inhibitor of poly(ADP-ribose) synthetase. 10 The monomeric structures of these two compounds, as well as their crystallographic arrangements, have already been a subject of several investigations.…”

Section: Introductionmentioning

confidence: 99%

Dimer formation in nicotinamide and picolinamide in the gas and condensed phases probed by infrared spectroscopy

Borba

Albrecht

Gómez‐Zavaglia

et al. 2008

Phys. Chem. Chem. Phys.

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Aggregation of nicotinamide (3-pyridine-carboxamide; NA) and picolinamide (2-pyridinecarboxamide; PA) has been investigated by matrix-isolation, supersonic jet and neat solid state infrared spectroscopy, complemented by DFT(B3LYP)/6-311++G(d,p) calculations. For both compounds, the most stable dimeric structure was shown to be the centrosymmetric dimer where two monomers in their most stable forms establish two NHÁ Á ÁOQC hydrogen bonds. The most stable structures of monomers of NA and PA were characterized in detail experimentally by matrix-isolation spectroscopy and theoretically (at both the DFT(B3LYP)/6-311++G(d,p) and MP2/6-311++G(d,p) levels). For nicotinamide, two conformers were found in the matrices, with ca. 80% of the total population adopting the E form. The monomers and dimers of PA and NA were also investigated by infrared spectroscopy of the studied compounds seeded in supersonic jet expansions. These studies revealed that the constraints on the vibrational dynamics in the PA dimer are different from those in the NA dimer. In the PA dimer, the vibrational energy flow out of the N-H stretching mode was shown to be accelerated substantially by the presence of a secondary intramolecular hydrogen bond. In the glassy state of both compounds, the centrosymmetric dimer seems to be the prevalent structure. In the neat crystalline state (KBr pellet), picolinamide keeps this type of dimeric structure as the constituting unit, whereas nicotinamide molecules assume a different arrangement where one of the NHÁ Á ÁOQC bonds is replaced by an NHÁ Á ÁN(ring) bond. The different crystallograpic structures which were formed by the compounds are reflected in the vibrational spectra of the solids. These observations are correlated with the molecular properties of NA and PA, in particular with the greater conformational mobility of NA compared with PA. This is ascribable to the absence in the NA molecule of the intramolecular NHÁ Á ÁN (ring) interaction, which exists in PA.

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“…Nicotinamide is the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD + ) and is considered to be an essential nutrient for cell growth and function (for review, see [26]). Recently, nicotinamide has been reported to exert a number of pharmacological effects including prevention of ATP depletion [22,24,42], inhibition of poly(ADP-ribose) polymerase (PARP) [22,23,42] and lipid peroxidation [10,23,29], antiinflammatory activity [40] and prevention of apoptosis [24,29]. In adult rats nicotinamide protects against both early necrotic cell death in the core and delayed apoptosis like cell death in the penumbra in stroke models [41].…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

Feng¹,

Paul²,

LeBlanc³

2006

Brain Research Bulletin

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Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F 2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

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Nicotinamide as a precursor for NAD+ prevents apoptosis in the mouse brain induced by tertiary-butylhydroperoxide

Cited by 85 publications

References 16 publications

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

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

Dimer formation in nicotinamide and picolinamide in the gas and condensed phases probed by infrared spectroscopy

Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

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