Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NICOTINIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed2006

Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation.

Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to the regulation of intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette to generate their characteristic Ca2+ signals but it is still unclear whether different messengers mediate different functions or whether they act in a redundant fashion. In this study, we compared the effects of nicotinic acid adenine dinucleotide phosphate (NAADP), a novel Ca2+-mobilizing messenger, with that of the prototypical messenger inositol trisphosphate on cytosolic Ca2+ levels and differentiation status of PC12 cells. We demonstrate that liposomal delivery of NAADP mediated release of Ca2+ from acidic Ca2+ stores and that this stimulus was sufficient to drive differentiation of the cells to a neuronal-like phenotype. In sharp contrast, cell fate was unaffected by more transient Ca2+ signals generated by inositol trisphosphate-evoked release of endoplasmic reticulum Ca2+ stores. Our data establish for the first time (i) the presence of novel NAADP-sensitive Ca2+ stores in PC12 cells, (ii) a role for NAADP in differentiation, and (iii) that Ca2+-dependent function can be messenger-specific. Thus, differential recruitment of intracellular Ca2+-mobilizing messengers and their target Ca2+ stores may represent a robust means of maintaining stimulus fidelity in the control of Ca2+-dependent cell function.

Animals↗
PubMed1993

Hypolipidemic effects of nicotinic acid in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which an amino acid substitution in apolipoprotein B-100 results in low-density lipoprotein (LDL) particles that bind poorly to the LDL receptor and accumulate in plasma. Patients with FDB described to date have been heterozygous for this disorder, and their plasma contains both normal and defective-binding LDL particles. We have evaluated the hypocholesterolemic effects of nicotinic acid (3 g/d) in four patients with FDB, and compared the response to that of nine patients with heterozygous familial hypercholesterolemia (FH). Concentrations of LDL decreased by 24% in patients with FDB and by 14% in patients with FH. These results support the view that drugs which reduce LDL synthesis may be particularly effective in the treatment of patients with FDB.

Adult↗
PubMed2006

Nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose regulate TRPM2 channels in T lymphocytes.

TRPM2 (previously designated TRPC7 or LTRPC2) is a Ca2+-permeable nonselective cation channel that contains a C-terminal enzymatic domain with pyrophosphatase activity, which specifically binds ADP-ribose. Cyclic ADP-ribose (cADPR) and hydrogen peroxide (H2O2) can facilitate ADPR-mediated activation of heterologously expressed TRPM2. Here, we show that the two Ca2+-mobilizing second messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) strongly activate natively expressed TRPM2 channels in Jurkat T cells. TRPM2 activation by both agonists can be partially suppressed by the ADPR antagonist adenosine monophosphate (AMP), which suggests that cADPR and NAADP lead to mobilization of endogenous ADPR presumably via metabolic conversion. The remaining channel activity is due to direct gating of TRPM2 by the two agonists and can be completely suppressed by 8-Br-cADPR, which suggests that cADPR and NAADP share a common binding site on TRPM2 that can regulate TRPM2 activity in synergy with ADPR. We conclude that cADPR and NAADP, in combination with ADPR, represent physiological co-activators of TRPM2 that contribute to Ca2+ influx in T lymphocytes and presumably other cell types that express this channel.

Cyclic ADP-Ribose↗
PubMed2000

Two different but converging messenger pathways to intracellular Ca(2+) release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate.

Hormones and neurotransmitters mobilize Ca(2+) from the endoplasmic reticulum via inositol trisphosphate (IP(3)) receptors, but how a single target cell encodes different extracellular signals to generate specific cytosolic Ca(2+) responses is unknown. In pancreatic acinar cells, acetylcholine evokes local Ca(2+) spiking in the apical granular pole, whereas cholecystokinin elicits a mixture of local and global cytosolic Ca(2+) signals. We show that IP(3), cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) evoke cytosolic Ca(2+) spiking by activating common oscillator units composed of IP(3) and ryanodine receptors. Acetylcholine activation of these common oscillator units is triggered via IP(3) receptors, whereas cholecystokinin responses are triggered via a different but converging pathway with NAADP and cyclic ADP-ribose receptors. Cholecystokinin potentiates the response to acetylcholine, making it global rather than local, an effect mediated specifically by cyclic ADP-ribose receptors. In the apical pole there is a common early activation site for Ca(2+) release, indicating that the three types of Ca(2+) release channels are clustered together and that the appropriate receptors are selected at the earliest step of signal generation.

Acetylcholine↗
PubMed2000

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 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.

Apoptosis↗
PubMed2004

Nicotinic acid adenine dinucleotide phosphate potentiates neurite outgrowth.

Ca(2+) regulates a spectrum of cellular processes including many aspects of neuronal function. Ca(2+)-sensitive events such as neurite extension and axonal guidance are driven by Ca(2+) signals that are precisely organized in both time and space. These complex cues result from both Ca(2+) influx across the plasma membrane and the mobilization of intracellular Ca(2+) stores. In the present study, using rat cortical neurons, we have examined the effects of the novel intracellular Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) on neurite length and cytosolic Ca(2+) levels. We show that NAADP potentiates neurite extension in response to serum and nerve growth factor and stimulates increases in cytosolic Ca(2+) from bafilomycin-sensitive Ca(2+) stores. Simultaneous blockade of inositol trisphosphate and ryanodine receptors abolished the effects of NAADP on neurite length and reduced the magnitude of NAADP-mediated Ca(2+) signals. This is the first report demonstrating functional NAADP receptors in a mammalian neuron. Interplay between NAADP receptors and more established intracellular Ca(2+) channels may therefore play important signaling roles in the nervous system.

Animals↗