Bottom-up proteomics analysis for adduction of the broad-spectrum herbicide atrazine to histone.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101134327 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-2650 (Electronic) Linking ISSN: 16182642 NLM ISO Abbreviation: Anal Bioanal Chem Subsets: MEDLINE

Original Publication: Heidelberg : Springer-Verlag, 2002-

Atrazine* ; Herbicides*/analysis; Humans ; Histones/chemistry ; Tandem Mass Spectrometry/methods ; Proteomics/methods

Histones are the major proteinaceous components of chromatin in eukaryotic cells and an important part of the epigenome. The broad-spectrum herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-1, 3, 5-triazine) and its metabolites are known to form protein adducts, but the formation of atrazine-histone adducts has not been studied. In this study, a bottom-up proteomics analysis method was optimized and applied to identify histone adduction by atrazine in vitro. Whole histones of calf thymus or human histone H3.3 were incubated with atrazine. After solvent-based protein precipitation, the protein was digested by trypsin/Glu-C and the resulting peptides were analyzed by high-resolution mass spectrometry using an ultra-high-performance liquid chromatograph interfaced with a quadrupole Exactive-Orbitrap mass spectrometer. The resulting tryptic/Glu-C peptide of DTNLCAIHAK from calf thymus histone H3.1 or human histone H3.3 was identified with an accurate mass shift of  +179.117 Da in atrazine incubated samples. It is deduced that a chemical group with an elemental composition of C 8 H 13 N 5 (179.1171 Da) from atrazine adducted with calf thymus histone H3.1 or human histone H3.3. It was confirmed by MS/MS analysis that the adduction position was at its cysteine 110 residue. Time- and concentration-dependent assays also confirmed the non-enzymatic covalent modification of histone H3.3 by atrazine in vitro. Thus, the potential exists that atrazine adduction may lead to the alteration of histones that subsequently disturbs their normal function.
(© 2023. Crown.)

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Keywords: Adduction; Atrazine; High-resolution Orbitrap mass spectrometry; Histone; Post-translational modification; UHPLC

0 (Histones)
QJA9M5H4IM (Atrazine)
0 (Herbicides)

Date Created: 20230120 Date Completed: 20230302 Latest Revision: 20240119

20240120

PMC9974708

10.1007/s00216-023-04545-6

36662240