Identification of Protein Thiazolidination as a Novel Molecular Signature for Oxidative Stress and Formaldehyde Exposure.
Chemical modifications of proteins have been well-documented to play important roles in normal cell physiology such as cell signaling and protein functions. They have also been demonstrated to be one of the milestones in the pathophysiology of many human diseases such as cancer, age-related pathology, and neurodegenerative disorders. Here, we report the initial identification of a novel protein modification, cysteine thiazolidination, through reaction with endogenous and exogenous formaldehyde with cysteine residues in proteins. Using an isotope-dilution liquid chromatography-tandem mass spectrometric (LC-MS3) method, we initiated the study by quantitating thioproline in formaldehyde-treated Escherichia coli (E. coli) protein. The study was then extended to quantitate thioproline in protein obtained from formaldehyde- and oxidant-exposed E. coli. Furthermore, N6-formyllysine, a well-defined formylation product between formaldehyde and lysine, was exploited in a comparative study to evaluate the relative reactivity and amount of cysteine thiazolidination in the reaction of formaldehyde with proteins. It is anticipated that cysteine thiazolidination may serve as a novel biomarker for oxidative stress and formaldehyde exposure.
Environmental Science Programs and ‡Department of Chemistry, The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong.
Jingjing
J
Liu
Environmental Science Programs and ‡Department of Chemistry, The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong.
K K Jason
KK
Chan
Environmental Science Programs and ‡Department of Chemistry, The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong.
Wan
W
Chan
D002138:Calibration; D002853:Chromatography, Liquid; D004926:Escherichia coli / Q000187:drug effects; D005557:Formaldehyde / Q000633:toxicity*; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000378:metabolism*
D011506:Proteins; D013844:Thiazoles; D005557:Formaldehyde