Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ADP-ribosylation of membrane G proteins is difficult to achieve in tissues that are rich in membrane-bound NAD glycohydrolase (NAD+ glycohydrolase, EC 3.2.2.5). For many animal species this problem can be surmounted by inhibiting NAD hydrolysis with a combination of the anti-tuberculous drug, isonicotinic acid hydrazide, and the NAD analog, 3-acetylpyridine adenine dinucleotide, which act synergistically. In their presence, the ADP-ribosylation of cholera and pertussis toxin substrates reach plateau levels even with only 10 microM NAD. Although 3-acetylpyridine adenine dinucleotide acts as a weak substrate for the toxins, it is simple to estimate its contribution to the ADP-ribosylation and thus to determine the total amount of ADP-ribosylation substrate present in a tissue sample. NAD glycohydrolases that are insensitive to isonicotinic acid hydrazide are also less sensitive to 3-acetylpyridine adenine dinucleotide, but may be inactivated by dithiothreitol. Isonicotinic acid hydrazide adenine dinucleotide, the product of an exchange reaction catalysed by NAD glycohydrolase, runs with NAD in most thin-layer chromatographic systems. It can be separated from NAD, and quantitated, if the chromatographic solvent contains benzaldehyde. Isonicotinic acid hydrazide itself inhibits NAD glycohydrolase. It need not first be converted into isonicotinic acid hydrazide adenine dinucleotide.
 ...
PMID:ADP-ribosylation of membrane proteins by bacterial toxins in the presence of NAD glycohydrolase. 283 27

[32P]ADP-ribosylation of membrane proteins catalyzed by either cholera toxin or pertussis toxin was markedly enhanced by NADP+. The effect was concentration dependent; with 20 microM [32P]NAD+ as a substrate maximal enhancement was obtained at a concentration of 0.5-1.0 mM NADP+ for rabbit and guinea-pig liver membranes and 0.1 mM NADP+ for human erythrocyte membranes. NADP+ appears to act by inhibiting the degradation of NAD+ by NAD+-glycohydrolase (NADase) present in membrane preparations, probably as an alternate substrate for the enzyme. Among inhibitors tested (NADP+, isonicotinic acid hydrazide, imidazole, nicotinamide, L-arginine methyl ester and HgCl2) to suppress the enzyme activity, NADP+ was the most effective and, at 10 mM, inhibited hepatic NADase activity by about 90%. The effect of NADP+ was much greater than that of other known effectors of ADP-ribosylation such as Mg2+ and phosphate, or the NADase inhibitors, isonicotinic acid hydrazide and isonicotinamide. In membranes which contain substantial activities of NADase the inclusion of NADP+ in the assay system is necessary to achieve maximal ADP-ribosylation of membrane proteins.
 ...
PMID:NADP+ enhances cholera and pertussis toxin-catalyzed ADP-ribosylation of membrane proteins. 302 76

Pertussis and cholera toxins failed to ADP-ribosylate G alpha s and G alpha i in membranes isolated from retinoic acid-differentiated HL-60 granulocytes, although G alpha i subunits were present. NAD was rapidly degraded in the presence of these membranes, primarily to ADP-ribose, to less than 10% of initial activity by 5 min. Metabolism of NAD was heat labile and inhibited by NADP, but not by imidazole or isonicotinic acid hydrazine. Pertussis toxin uncoupled LTB4 receptors from G proteins in intact retinoic acid-differentiated HL-60 cells. Retinoic acid differentiation stimulates expression of a unique NAD-glycohydrolase activity in HL-60 granulocytes which prevents ADP-ribosylation in isolated membranes, but not intact cells.
 ...
PMID:Rapid degradation of NAD by retinoic acid-differentiated HL-60 granulocyte membranes prevents ADP ribosylation. 838 92