Disease relevance of Nat1

• Genes for the 290 amino acid, 33-34 kDa cytosolic acetyltransferases (NAT1* and NAT2*) from rat and hamster were cloned and expressed in Escherichia coli [1].
• Cells were aspirated from tumors with low metastatic potential (following subcutaneous inoculation of 10(6) tumor cells the H, G and AT-1 variants had less than 5% metastases; AT-2 had 5-20%) and were compared to the electrophoretic mobility of cells aspirated from highly metastatic tumors (MAT-LyLu, MAT-Lu, AT-3 had greater than 90% metastases) [2].
• In this study, we reported the effects of vitamin C on arylamine N-acetyltransferase (NAT) activity and DNA adduct formation in rat glial tumor cell line (C6 glioma) [3].

High impact information on Nat1

• A complementary DNA (cDNA) library from the anaplastic nonmetastasizing subline AT-1 was used for a differential hybridization analysis, using probes derived from mRNAs of the AT-1 and the metastasizing MAT-LyLu subline [4].
• In 2 weakly metastatic cell lines (AT-1 and AT-2), p9Ka transcript amounts were, respectively, 6.29 +/- 0.74 and 5.55 +/- 1.11 times that detected in the G cells [5].
• The data also indicate that at low substrate concentrations, NAT1 would apparently play the predominant role in vivo in N-acetylation and N,O-acyltransfer of aromatic amine derivatives, including their metabolic activation to DNA-reactive agents [1].
• These data suggest that steroidogenesis may be modulated by angiotensin peptides that act in part through intracellular AT1 receptors [6].
• Quinapril, ZPP, PCMS, and PMSF, as well as losartan and PD-123319, the angiotensin receptor type 1 (AT1) and type 2 (AT2) receptor antagonists, were used in progesterone production studies [6].

Chemical compound and disease context of Nat1

• Carmustine and lomustine are nitrosourea antitumor chemotherapeutic agents which were used to determine whether or not they could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adducts in rat glial tumor cell line (C6 glioma) [7].

Biological context of Nat1

• This result is consistent with substrate specificity data indicating that N-OH-AAF is a much better acetyl donor for hamster NAT1 than NAT2 [8].
• The low metastatic sublines G, AT-1, and AT-2 had 0.32 +/- standard deviation 0.10, 0.38 +/- 0.12, and 0.14 +/- 0.05 sister chromatid exchanges per chromosome, respectively [9].
• Pinocytosis failed to distinguish sublines of high (AT-3 63.5 +/- standard error 4.1 mean channel number, MAT-LyLu 63.2 +/- 6.3, MAT-Lu 64.3 +/- 5.6) and low (G 33.5 +/- 1.2, AT-1 63.5 +/- 4.1, AT-2 58.4 +/- 3.6) (rank p = 0.38) metastatic potential but correlated strongly with visually graded membrane ruffling (r = 0.95, p = 0.003) [10].
• None of the phosphorylation modulators led to a significant change in NAT1 or NAT2 activities [11].
• The effect of SLO pretreatment of rats on cytochrome P-450-catalyzed tolbutamide hydroxylation and NAT activities toward PA (a substrate for NAT1), and p-aminobenzoic acid (a substrate for NAT2) was examined ex vivo [12].

Anatomical context of Nat1

• We conclude that cGMP synthesis in cultured podocytes is modulated by angiotensin II and that two adversely acting receptors, AT1 and AT2 are involved in this effect [13].
• The rat adrenal gland contains both AT-1 and AT-2 receptors in the ratio of approximately 3:2 in the cortex and 1:9 in the medulla [14].
• The pharmacological specificity obtained in kidney, adrenal cortex and adrenal medulla, superior colliculus, and nucleus of the solitary tract produces specificity patterns which confirm the assignments of AT-1 and AT-2 receptors described above [14].
• Translocation of AT1- and AT2-Receptors by Higher Concentrations of Angiotensin II in the Smooth Muscle Cells of Rat Internal Anal Sphincter [15].
• NAT1 mRNA expression in locus coeruleus is decreased in 4-week alloxan-icv treated rats (-35%) and increased in A1 cell group of 1- (+19%) and 4- (+14%) week streptozotocin-icv treated rats [16].

Associations of Nat1 with chemical compounds

• In most of the sublines with a more advanced state of progression (i.e., the moderately differentiated, moderately fast growing HI-M; the poorly differentiated, faster growing HI-F; and the anaplastic, very fast growing AT-1, AT-2, and MAT-Lu tumors), however, no expression of keratin specific for luminal cells was detected [17].
• Monomorphic (NAT1) and polymorphic (NAT2) activities were determined using N-acetylprocainamide and N-acetamidobenzoic acid formation, respectively [18].
• Serum melatonin levels reflected the circadian pattern of the NAT1 activity, without, however, showing any quantitative differences between the two strains [19].
• However, while levels of Ang II type 1 (AT1) receptor increased over time after LPS injection, those of Ang II type 2 (AT2) receptor were downregulated, (3) data of NO system (NO-NOS), the key vasodilator, were the most intriguing [20].
• Effect of streptolysin-O-on rat hepatic acetyl coenzyme-A: arylamine N-acetyltransferase and cytochrome P-450 2B 1/2 activities ex vivo [12].

Physical interactions of Nat1

• The reducing agent dithiothreitol decreased the binding to AT-1 receptors and enhanced the binding to AT-2 receptors [14].

Other interactions of Nat1

• Cloning, sequencing and expression of NAT1 and NAT2 encoding genes from rapid and slow acetylator inbred rats [21].
• To investigate melatonin synthesis and secretion in LEW/N and F344/N rats, we examined the diurnal activity of pineal arylalkylamine N-acetyltransferase (NAT1), the rate-limiting enzyme in melatonin biosynthesis, which demonstrates circadian rhythmicity, as well as the diurnal levels of serum melatonin, in both strains [19].
• The inducers led to the expected increases in CYP1A1 and CYP1A2 but the NAT1 and NAT2 activities remained unchanged [11].

Analytical, diagnostic and therapeutic context of Nat1

• The nonmetastatic G, occasionally metastatic AT-1 and AT-2, and highly metastatic AT-3 and MAT-Lu Dunning sublines, and normal dorsal prostate were grown in culture and filmed by time-lapse videomicroscopy [22].
• Size-exclusion HPLC chromatograms of NAT1 activity revealed similar patterns in both rat strains.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• Our study shows that the N-acetyl transferases NAT1 or NAT2, the catalysts responsible for the formation of the highly reactive N-acetoxy derivatives of N-hydroxylated aromatic amines, are not responsible for the drastic decrease in arylamine genotoxicity after treatment of the metabolizing system with protein phosphatase inhibitors [11].
• Angiotensin II (Ang II) receptor binding was localized in rat adrenal gland, kidney, and brain by in vitro autoradiography using the antagonist analogue 125I-[Sar1, Ile8]Ang II and differentiated into type I (AT-1) and type II (AT-2) subtypes using unlabelled non-peptide antagonists specific for Ang II subtypes [14].
• Northern blot analysis was carried out to measure the cerebral tissue content of a novel translational repressor (NAT-1) and another thyroid hormone-responsive (THR) mRNA [23].

References