Disease relevance of Indolylacetonitrile

• We cloned and sequenced the gene for nitrilase (EC 3.5.5.1), which catalyzes the hydrolysis of indole-3-acetonitrile to indole-3-acetic acid, from Alcaligenes faecalis JM3 [1].
• Nitrosation of indole-3-carbinol, indole-3-acetonitrile and indole, hydrolysis products of an indolylglucosinolate, resulted in formation of nitrosated products, which were directly mutagenic to Salmonella typhimurium TA100 [2].

High impact information on Indolylacetonitrile

• Benzyl isothiocyanate, beta-naphthoflavone, coumarin, alpha-angelicalactone, disulfiram, indole-3-carbinol and indole-3-acetonitrile induced increased glutathione (GSH) S-transferase activity in the liver and small intestine in female ICR/Ha mice [3].
• The nitrilase genes encode very similar proteins that hydrolyze indole-3-acetonitrile to the phytohormone indole-3-acetic acid in vitro, and three of the four genes are tandemly arranged on chromosome III [4].
• In Cruciferae, including Brassicaceae, indole-3-acetic acid is synthesized from indole-3-acetonitrile by nitrilase, after indole-3-acetonitrile is formed from tryptophan via indole-3-acetaldoxime or indole glycosinolates as the intermediate [1].
• Despite the relatively high homology to Arabidopsis NIT4, ZmNIT2 shows no activity toward beta-cyano-alanine, the substrate of Arabidopsis NIT4, but instead hydrolyzes indole-3-acetonitrile (IAN) to indole-3-acetic acid (IAA) [5].
• The Nitrilase ZmNIT2 converts indole-3-acetonitrile to indole-3-acetic acid [5].

Biological context of Indolylacetonitrile

• Collectively, these data prove the ability of nitrilase II to convert low micromolar levels of indole-3-acetonitrile to indole-3-acetic acid in vivo, even when expressed at subphysiological levels thereby conferring a high-auxin phenotype upon transgenic plants [6].
• The modulating effects of pretreatment of cultured cells with indole-3-carbinol (I3C) and indole-3-acetonitrile (I3A) on the induction of sister-chromatid exchanges (SCEs) by mutagens from different chemical classes were investigated [7].
• Both mutagenicity data and measurements by high-performance liquid chromatography using a photohydrolysis detector indicated that the nitrosation products of indole-3-acetonitrile, indole-3-carbinol and indole were more stable at pH 8 than at pH 2 [8].

Anatomical context of Indolylacetonitrile

• Other glucobrassicin metabolites, diindolylmethane and indole-3-acetonitrile, also had some inducing effect in the liver but no effect in the intestine, while ascorbigen significantly induced ERR deethylation in the small and large intestine but had no effect on hepatic MFO activity [9].
• Treatment of rat hepatocytes with indole-3-acetonitrile and 3,3'-diindolylmethane, but not I3C and indole-3-carboxaldehyde, enhanced EROD activity and halved testosterone 16 alpha- and 2 alpha-hydroxylation [10].

Associations of Indolylacetonitrile with other chemical compounds

• Indole-3-acetamide, indole-3-acetonitrile and indole-3-acrylic acid exhibited a potent inhibition for mammalian tryptophan 2,3-dioxygenase, while they moderately inhibited the pseudomonad enzyme [11].
• Tryptanthrin (1), indole-3-acetonitrile (2) and p-coumaric acid methylester (3) were isolated from the aerial parts of Isatis tinctoria L [12].

Gene context of Indolylacetonitrile

• Introduction of Arabidopsis NIT2 into tobacco conferred IAN-mediated growth inhibition, probably due to hydrolysis of IAN to IAA, while ectopic expression of TNIT4A had little effect on the sensitivity of transgenic plants to IAN [13].
• This, as well as immunological evidence for the presence of a nitrilase-like protein in the complex, suggests the reaction to proceed via the intermediate indole-3-acetonitrile [14].
• Elicitation experiments in tissues of Brassica juncea and B. rapa showed that indole-3-acetonitrile was an inducible metabolite produced in leaves and stems of B. juncea but not in B. rapa [15].

Analytical, diagnostic and therapeutic context of Indolylacetonitrile

• No DNA adducts were detected after treatment with the non-nitrosated compound indole-3-acetonitrile both in vivo and in vitro [16].
• Using a combination of high-performance liquid chromatography, monoclonal-antibody based enzyme-linked immunosorbent assay and mass spectroscopy, it was shown that the isolated cDNA clone encodes an enzymatically active nitrilase which is able to convert indole-3-acetonitrile to the plant growth hormone, indole-3-acetic-acid [17].

References