Effects Of 6-aminonicotinamide Research Articles

Effects of neurotoxin 6-aminonicotinamide on levels of enzyme activities and metabolites in quail plasma

Effects of 6-aminonicotinamide (6-AN) on the levels of proteins, metabolites and enzyme activities in the plasma of Japanese quail were investigated. The concentrations of soluble proteins in the pectoral and hindlimb muscle of the 6-AN treated and the pair-fed groups were significantly reduced compared to the control group. In the plasma, the levels of total proteins and albumin were not affected, but the levels of globulin were significantly lower than those of the control and pair-fed groups. In contrast, the levels of glucose and creatine were significantly elevated. Cellulose acetate gel electrophoresis showed that 6-AN induced a new synthesis of prealbumin and also increased the levels of β-globulin relative to the control and pair-fed groups. In contrast, the levels of γ-globulin were markedly lower than those of the control group, whereas the levels of α-globulin were not affected. The specific activity of alkaline phosphatase of the 6-AN group was significantly lower than that of the control and pair-fed groups and that of aspartate aminotransferase only lower than that of the control group but not the pair-fed group. The specific activities of creatine phosphokinase and lactate dehydrogenase of the 6-AN group were the greatest among the three groups, whereas those of the pair-fed group were greater than those of the control group. The results suggest that 6-AN may interfere with the proper maintenance of energy charges and the immune system function.

Effects of 6-aminonicotinamide on levels of soluble proteins and enzyme activities in various tissues of Japanese quail

The effects of 6-aminonicotinamide (6-AN) on the levels of soluble proteins and enzyme activities in various tissues of Japanese quail were investigated. SDS-polyacrylamide gel electrophoresis showed that the soluble proteins with molecular masses corresponding to 160.4 and 52.5 kDa were either missing or present at lower concentrations in the brain of the 6-AN treated group compared to those in the control group. The soluble liver proteins with molecular masses 200, 120 and 70.5 kDa were missing in the treated group compared to those in the control while those of a molecular mass 15.1 kDa were found to be present at higher concentrations. Similarly, treatment with 6-AN decreased the concentration of soluble proteins in pectoral muscle with molecular masses 92.3, 54.5, 43.5, 41.2, 34.5, 27.5, 20.1 and 17.5 kDa and increased those with molecular masses 96.5, 37.7, 25.0, 19.3, 16.6, 13.8 and 10.8 kDa. In the heart, soluble proteins with molecular mass 84.6 kDa were increased. There was a marked reduction in the treatment group in the concentration of NAD in pectoral muscle but not in other tissues. A similar observation was also made with total RNA levels. The specific activity of malic enzyme was markedly increased by 6-AN treatment in the kidney and pectoral muscle but reduced in the liver. 6-Phosphogluconate dehydrogenase and lactate dehydrogenase activities were markedly reduced in the liver. Glyceraldehyde-3-phosphate dehydrogenase activity was significantly decreased in liver and pectoral muscle. NAD glycohydrolase activity was markedly decreased in pectoral muscle. Acetylcholinesterase activity was markedly reduced in liver but was enhanced in pectoral muscle. The results suggest that the metabolic actions of 6-AN are specific for certain proteins in the liver and muscle with the effect being most pronounced in muscle. The effects are also quite distinct from those shown by its analogue 3-acetylpyridine.

Effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide metabolism

The purpose of this study was to determine if the cytotoxic effects of 6—aminonicotinamide are solely the result of an inhibition of poly(ADP-ribose) synthesis. The effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide concentrations were compared with the effect of 3-aminobenzamide, a more potent inhibitor of poly(ADP-ribose) synthesis. The growth of L1210 cells was not inhibited by 1 mM 3-aminobenzamide and was only slightly inhibited by 5 mM 3-aminobenzamide even though poly(ADP-ribose) synthesis, as measured by the N-methyl N-nitrosourea induced depletion of NAD +, was inhibited substantially. In contrast, 6-aminonicotinamide was found to be a potent inhibitor of L1210 and CHO cell growth. A 5 mM concentration of 3-aminobenzamide had no effect on purine and pyrimidine ribonucleotide concentrations or on the ATP to ADP ratio, but it did cause a slight elevation of NAD +. 6-Aminonicotinamide at 0.01 mM caused a depletion of purine and pyrimidine nucleotides and NAD + as well as a reduction in the ATP to ADP ratio. 6-Aminonicotinamide at 1 mM caused a substantial inhibition of purine nucleotide synthesis from [ 14C] glycine but did not stimulate ATP breakdown. We conclude that inhibition of poly(ADP-ribose) synthesis caused little growth inhibition in itself and that the effects of 6-amininicotinamide on nucleotide metabolism were sufficient to produce an inhibition of both cell growth and DNA repair.

Hyperglycemia and inhibition of glucose-induced insulin release in 6-aminonicotinamide treated rats

The effects of 6-aminonicotinamide (6-AN) on blood glucose and insulin release were studied in rats. 6-AN at 4mg/100g body weight slowly raised blood glucose concentrations to a significantly higher level than the control values 6 hours after an intraperitoneal injection. At this time severe glucose intolerance and low IRI response were noticed during an intravenous glucose tolerance test. Adrenalectomized rats replaced by hydrocortisone also presented hyperglycemia, glucose intolerance and low IRI response during IVGTT under treatment with 6-AN but to a lesser extent than in the intact rats. In in vitro experiments, decreased insulin release from the perfused pancreata of rats pretreated with 6-AN was found both in the 1st and 2nd phases of response to glucose stimulation. These data indicate that 6-AN-induced hyperglycemia is attributed to the inhibition of insulin release in adrenalectomized rats except for the hypothetical effect of 6-AN which diminishes an action of insulin on cellular glucose transport.

Effects of 6-aminonicotinamide on growth and acetylcholinesterase activity during differentiation of neuroblastoma cells in vitro

Addition of 6-AN (0.01 mg/ml) to growing cultures of C-1300 neuroblastoma cells strongly reduced cell division. This growth inhibition was accompanied by a higher cell volume and a lower protein content per cell as compared to controls. Concurrently the specific activity of AChE increased markedly incontrols and 6-AN-treated cultures. During the experimental periods the specific activity of AChE was significantly higher after 6-AN. Morphologically, 6-AN-treated cultures showed characteristic signs of differentiation, i.e. enlarged, flattened cells with long branched processes. The described effect of 6-AN on growth and differentiation of neuroblastoma cells was less pronounced if cells received the antimetabolite after a subcultivation period of 5 days.

Effects of 6-aminonicotinamide on abolition and induction of audiogenic seizures

Effects of 6-aminonicotinamide on abolition and induction of audiogenic seizures

A cytoplasmically transmitted, diet-dependent difference in response to the teratogenic effects of 6-aminonicotinamide.

The frequency of congenital cleft palate produced by maternal treatment with 6-aminonicotinamide during pregnancy is lower in the C57BL/6J than in the A/J inbred mouse strain. In the C57BL/6J strain the frequency is lower when the mothers are maintained on Purina Lab Chow than when they are on Breeder Chow. A/J females do not show this effect of diet. There is a matroclinous reciprocal cross difference in frequency of induced cleft palate which persists in the back-cross when the F(1) mothers are maintained on Lab Chow but not on Breeder Chow.

6-AMINONICOTINAMIDE AND THE RADIOSENSITIVITY OF HUMAN LIVER CELLS IN CULTURE.

The effects of 6-aminonicotinamide on the radiosensitivity of human foetal liver cells and Ehrlich ascites tumor cells were studied using x rays in separate experiments. 6-Aminonicotinamide was found to have a sensitizing effect on the radiosensitivity of liver cells when measured by reproductive integrity, but none when measured by chromosome damage; no effect was observed ih the chromosome damage in tumor cells. The reproduction and chromosome experiments differed from each other in that 6-aminonicotinsmide was added before the cells were allowed to attach to glass in the former, while the order was reversed in the latter. It is concluded that 6-aminonicotinamide reduces the plating efficiency. (D.L.C.)