Disease relevance of nadide

• Upon treatment with pertussis toxin and [32P] NAD, purified adipocyte membranes from ob/ob mice incorporated twice as much radioactivity per unit membrane protein than those from +/+ mice in the 40,000-42,000 region [1].
• Furthermore, pertussis toxin was able to catalyze the labeling of a neuroblastoma membrane protein in vitro using [32P] NAD+ under conditions similar to those by which attenuation of the cannabimimetic inhibition of adenylate cyclase could be demonstrated [2].
• Second-strand DNA was synthesized by employing the replacement synthesis method using Escherichia coli RNase H, E. coli DNA polymerase I, E. coli DNA ligase, and beta-NAD+ [3].
• We measured this protein in erythrocyte membranes of ten patients with pseudohypoparathyroidism (PHP), using assays of its biochemical activity and of its susceptibility to radiolabeling in the presence of 32P-NAD and cholera toxin [4].

High impact information on nadide

• This sensitivity of LTRPC2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (beta-NAD+) to the MutT motif [5].
• BFA had no effect on cell surface binding and endocytosis of a functional fluorescent CT analog or on the dose dependency of CT induced 32P-NAD ribosylation of Gs alpha in vitro [6].
• Similar to our observations with pierisin-1 and -2, crude extracts from the clams Meretrix lamarckii, Ruditapes philippinarum, and Corbicula japonica incubated with calf thymus DNA and beta-NAD resulted in production of N(2)-(ADP-ribos-1-yl)-2'-deoxyguanosine [7].
• ADP-ribosylation with 32P-NAD and PTX of choroid plexus revealed an intense labeling at the 40 kDa level in addition to the known PTX-substrates at 41 kDa (Gi alpha) and 39 kDa (Go alpha) [8].
• To test whether the redox state might have an effect on AMPK activity, we examined the effect of beta-NAD and NADH on this enzyme [9].

Chemical compound and disease context of nadide

• Furthermore, pertussis toxin treatment of membrane fragments from these cells did not result in labeling of the 41,000-dalton alpha-subunit of Ni with ADP ribose from [32P] NAD, indicating maximal ADP ribosylation of Ni by prior treatment of cells with pertussis toxin [10].

Biological context of nadide

• 2. In inside-out recordings, beta-NAD+ (0.05-1.0 mM) induced the appearance of a channel characterized by extremely slow kinetics, with mean open times in the range of seconds [11].
• Exposure of the labelled proteins to phosphodiesterase yielded 32P-AMP, and hydrolysis with NaOH yielded 32P-NAD+ [12].
• Botulinum neurotoxin A (BoNTA, 0.1 micromol/l) abolished the evoked release of NE, ATP, and beta-NAD at 4 Hz, suggesting that at low levels of neural activity, release of these neurotransmitters results from N-ethylmaleimide-sensitive factor attachment protein receptor/synaptosomal-associated protein of 25 kDa-mediated exocytosis [13].
• Our data indicated that lipopolysaccharide (1mg/kgb.w., i.p.)-evoked systemic inflammation enhanced PARP-1 activity in the mouse brain, leading to the lowering of beta-NAD(+) concentration, to translocation of apoptosis inducing factor from mitochondria to the nucleus, and to enhanced lipid peroxidation [14].
• The cyclase converts beta-NAD to cADPR, a calcium mobilizing second messenger involved in fertilization, insulin secretion, and muscle contraction [15].

Anatomical context of nadide

• In conclusion, we detected constitutive and nerve-evoked overflow of beta-NAD, cADPR, and ADPR in vascular and non-vascular smooth muscles, beta-NAD being the prevailing compound [16].
• We report here that incubation of beta-NAD+ with cell-free extracts of several rat tissues (including pituitary gland) generates a product which releases intracellular Ca2+ stores in permeabilized rat pituitary GH4C1 cells [17].
• Both of these electrical changes could be induced by perfusion, through a patch pipette, of nanomolar concentrations of cADPR or its precursor, beta-NAD, into unfertilized oocytes [18].
• MMS produces more cell membrane damage than MNNG at equitoxic doses. beta-NAD+ is the substrate for ADP-ribosylation and normally does not freely diffuse into cells. beta-NAD+ had no significant effect on SCE induction in intact cells or in cells treated with either 3AB or alkylating agent alone [19].
• 1. Whole-cell voltage-clamp recordings were used to study the characteristics of a non-selective cation current, activated by intracellular beta-NAD+, present in CRI-G1 insulin-secreting cells [20].

Associations of nadide with other chemical compounds

• ADP-ribosyl cyclase catalyzes the synthesis of two structurally and functionally different Ca2+ releasing molecules, cyclic ADP-ribose (cADPR) from beta-NAD and nicotinic acid-adenine dinucleotide phosphate (NAADP) from beta-NADP [18].
• Microinjection of beta-NAD+ into fura-2-loaded beta-cells did not increase [Ca2+]i nor did it alter the cells' subsequent [Ca2+]i response to glucose [21].
• 6. The flavin fluorescence is partially quenched, and the visible and near-ultraviolet circular dichroism spectrum is changed by beta-NAD+ [22].
• Capsaicin (10 micromol/l) increased both the resting and EFS-evoked overflow of beta-NAD+ [23].
• The EFS-evoked release of beta-NAD+ was frequency dependent and is reduced in the presence of tetrodotoxin (TTX; 0.3 micromol/l), omega-conotoxin GVIA (50 nmol/l), and botulinum neurotoxin A (BoNT/A; 100 nmol/l), but remained unchanged in the presence of guanethidine (3 micromol/l), omega-agatoxin IVA (50 nmol/l), or charbachol (1 micromol/l) [23].

Gene context of nadide

• Sir2 enzymes have been shown to couple substrate deacetylation and beta-NAD(+) cleavage to the formation of O-acetyl-ADP-ribose, a newly described metabolite [24].
• Cyclic adenosine diphosphate ribose (cADPR) is a potent endogenous calcium-mobilizing agent synthesized from beta-NAD+ by ADP-ribosyl cyclases in sea urchin eggs and in several mammalian cells (Galione, A., and White, A. (1994) Trends Cell Biol. 4, 431 436) [25].
• To provide evidence for the identification of the 170-kDa band as DNA topoisomerase II, the enzyme was immunoprecipitated from isolated nuclei incubated with 32P-NAD and a labeled peptide of 170 kDa was observed [26].
• The tissue superfusates collected during EFS also contained the beta-NAD+ metabolite ADPR (0.35 +/- 0.2 fmol/mg tissue) but not cyclic ADPR (cADPR) [23].
• We determined the capacity of kidney and its components for synthesis of cADPR from beta-NAD, that is catalyzed by enzyme ADP-ribosyl cyclase, and enzymatic inactivation that is catalyzed by cADPR-glycohydrolase [27].

Analytical, diagnostic and therapeutic context of nadide

• The level of alpha s as measured both by ADP-ribosylation with cholera toxin in the presence of 32P-NAD and by immunoblotting with specific antibody to alpha s decreased by 3-fold in cells grown in media supplemented with LPDS compared with control [28].
• A detailed HPLC fraction analysis determined that nicotinamide adenine dinucleotide (beta-NAD+; 7.0 +/- 0.7 fmol/mg tissue) is the primary nucleotide that contributes to the formation of eADPR [23].
• Isolated nuclei or nucleoli were labeled with 32P-NAD; then the nucleolar proteins were analyzed by 1-dimensional and 2-dimensional polyacrylamide gel electrophoresis (PAGE) and modified proteins were detected by autoradiography [29].
• A robust analytical method, using reversed-phase high-performance liquid chromatography with gradient elution and photodiode-array detection, was used to measure six purines and beta-NAD+ in acid-soluble extracts of samples taken from six different regions of human term placenta [30].
• A consistently moderate inhibition was found when fragments were previously incubated with toxin in the presence of beta-NAD but not in its absence of after treatment with non-activated toxin [31].

References