Synthesis of N pi-methylhistamine and N alpha-methylhistamine by purified rabbit lung indolethylamine N-methyltransferase.

Herman, Karl; Bowsher, Ronald R.; Henry, David P.

doi:10.1016/s0021-9258(17)39030-0

Cited by 25 publications

(9 citation statements)

References 48 publications

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“…The most upregulated proteins included molecules previously associated with asthma (CLCA1 or gob-5, VCAM1, CTSS) and specific components of the mucosal/IgA immune system (IgA constant region, and nonpolymorphic H-2 class I-Q10a). The two most downregulated proteins (XRCC1 and INMT) are thought to function in repairing or limiting tissue damage, specifically that involving single-strand DNA breaks, xenobiotics, or endogenous amino, sulfo, or selenium compounds. , Overall, the protein changes in the airways of sensitized, GSH–MDI exposed mice are distinct compared with those induced by other respiratory tract exposures − and might serve as biomarkers of MDI exposure and/or asthma.…”

Section: Discussionmentioning

confidence: 99%

Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation

Wisnewski

Liu

Colangelo

2015

Chem. Res. Toxicol.

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Isocyanates have been a leading chemical cause of occupational asthma since their utility for generating polyurethane was first recognized over 60 years ago, yet the mechanisms of isocyanate asthma pathogenesis remain unclear. The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. In naïve mice, a mixture of GSH reaction products with the chemical allergen, methylene-diphenyl diisocyanate (MDI), induced innate immune responses, characterized by significantly increased airway levels of Chitinase YM-1 and IL-12/IL-23β (but not α) subunit. However, in mice immunologically sensitized to MDI via prior skin exposure, identical GSH–MDI doses induced substantially greater inflammatory responses, including significantly increased airway eosinophil numbers and mucus production, along with IL-12/IL-23β, chitinases, and other indicators of alternative macrophage activation. The “self”-protein albumin in mouse airway fluid was uniquely modified by GSH–MDI at position 414K, a preferred site of MDI reactivity on human albumin. The 414K–MDI conjugation appears to covalently cross-link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)–MDI or asymmetric (S,N′-linked) bis(GSH)–MDI conjugates. Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation

Wisnewski

Liu

Colangelo

2015

Chem. Res. Toxicol.

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“…INMT catalyzes the N-methylation of indolamines, aromatic alkylamines, indolamines, amines, nicotine and structurally related compounds [5][6][7]. As N-methylation of endogenous and xenobiotic compounds leads to the degradation of the compounds [5], INMT may promote CRPC growth and development by detoxification of the anticancer metabolites that are produced in cancer cells and/or existed in tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the basic structures of the known substrates of INMT [5][6][7], we designed the experimental procedures for analyzing and comparing the potential substrates of INMT in tumor tissues. INMT-KD and control Myc-CaP castration-resistant allograft tumors were homogenized.…”

Section: Screening the Endogenous Substrates Of Inmt In Crpcmentioning

confidence: 99%

“…Indolethylamine-N-methyltransferase (INMT), also named as aromatic alkylamine N-methyltransferase, indolamine N-methyltransferase, arylamine N-methyltransferase, thioether S-methyltransferase, amine N-methyltransferase, nicotine N-methyltransferase, is a methyltransferase that transfers one or more methyl groups from the methyl donor S-adenosyl-l-methionine (SAM) to the substrates [5][6][7]. INMT functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide [8].…”

mentioning

confidence: 99%

“…INMT functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide [8]. INMT also catalyzes the N-methylation of indoles such as tryptamine and structurally related compounds [5][6][7]. As indicated in its aliases, INMT also catalyzes the (N)-methylation of many other different substrates, however, these methylation substrates are largely unknown.…”

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confidence: 99%

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Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer

Zhong

Jeong

Huang

et al. 2021

J Exp Clin Cancer Res

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Background Castration-resistant prostate cancer (CRPC) is associated with a very poor prognosis, and the treatment of which remains a serious clinical challenge. Methods RNA-seq, qPCR, western blot and immunohistochemistry were employed to identify and confirm the high expression of indolethylamine N-methyltransferase (INMT) in CRPC and the clinical relevance. Chip assay was used to identify Histone-Lysine N-Methyltransferase (SMYD3) as a major epigenetic regulator of INMT. LC-MS/MS were used to identify new substrates of INMT methylation in CRPC tissues. Gene knockdown/overexpression, MTT and mouse cancer models were used to examine the role of INMT as well as the anticancer efficacy of INMT inhibitor N,N-dimethyltryptamine (DMT), the SMYD3 inhibitor BCl-12, the selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC), and the newly identified endogenous INMT substrate Bis(7)-tacrine. Results We found that the expression of INMT was highly increased in CRPC and was correlated with poor prognosis of clinical prostate cancer (PCa). INMT promoted PCa castration resistance via detoxification of anticancer metabolites. Knockdown of INMT or treatment with INMT inhibitor N,N-dimethyltryptamine (DMT) significantly suppressed CRPC development. Histone-Lysine N-Methyltransferase SMYD3 was a major epigenetic regulator of INMT expression, treatment with SMYD3 inhibitor BCl-121 suppressed INMT expression and inhibits CRPC development. Importantly, INMT knockdown significantly increased the anticancer effect of the exogenous selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC) as well as the endogenous metabolite Bis(7)-tacrine. Conclusions Our study suggests that INMT drives PCa castration resistance through detoxification of anticancer metabolites, targeting INMT or its regulator SMYD3 or/and its methylation metabolites represents an effective therapeutic avenue for CRPC treatment.

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Determination of histamine, 1-methylhistamine and N-methylhistamine by capillary electrophoresis with micelles

Nishiwaki

Kuroda

Inoue

et al. 2000

Biomed. Chromatogr.

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Urinary histamine and Ngamma-methylhistamine (1-MH), a histamine metabolite, are highly correlated with histamine in plasma. Therefore, allergic reactions can be examined by determination of histamine and 1-MH in urine. We separated histamine, 1-MH and Nalpha-methylhistamine (N-MH) by capillary electrophoresis with UV detection at 210nm, using borate buffer (pH 9) containing 100 mM SDS. The absolute detection limits were 200, 100 and 50 pg for histamine, 1-MH and N-MH, respectively. To purify histamine 1-MH and N-MH in urine, a silica cartridge was used. Recovery rates of histamine, 1-MH and N-MH in physiological saline were 90.0, 91.4 and 95.4%, respectively. We measured histamine and 1-MH levels in urine from a normal female volunteer before and after a meal, and a male bronchial asthma patient. The results showed clearly that the concentrations of histamine and its metabolite rose after eating or asthma attack. N-MH was not detected in the urine.

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Synthesis of N pi-methylhistamine and N alpha-methylhistamine by purified rabbit lung indolethylamine N-methyltransferase.

Cited by 25 publications

References 48 publications

Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation

Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation

Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer

Determination of histamine, 1-methylhistamine and N-methylhistamine by capillary electrophoresis with micelles

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