Global Discovery and Temporal Changes of Human Albumin Modifications by Pan-Protein Adductomics: Initial Application to Air Pollution Exposure
- Joshua W. Smith
Joshua W. SmithDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United StatesMore by Joshua W. Smith
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- Robert N. O’Meally
Robert N. O’MeallyDepartment of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United StatesMore by Robert N. O’Meally
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- Sean M. Burke
Sean M. BurkeDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United StatesMore by Sean M. Burke
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- Derek K. Ng
Derek K. NgDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, United StatesMore by Derek K. Ng
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- Jian-Guo Chen
Jian-Guo ChenQidong Liver Cancer Institute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, Jiangsu 226200, P. R. ChinaMore by Jian-Guo Chen
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- Thomas W. Kensler
Thomas W. KenslerPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United StatesMore by Thomas W. Kensler
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- John D. Groopman
John D. GroopmanDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United StatesMore by John D. Groopman
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- Robert N. Cole*
Robert N. Cole*[email protected]Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United StatesMore by Robert N. Cole
Abstract
Assessing personal exposure to environmental toxicants is a critical challenge for predicting disease risk. Previously, using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys34 and ambient air pollutant levels (Smith et al., Chem. Res. Toxicol. 2021, 34, 1183). These results provided the foundation to explore modifications at other sites in HSA to reveal novel adducts of complex exposures. Thus, the Pan-Protein Adductomics (PPA) technology reported here is the next step toward an unbiased, comprehensive characterization of the HSA adductome. The PPA workflow requires <2 μL serum/plasma and uses nanoflow-liquid chromatography, gas-phase fractionation, and overlapping-window data-independent acquisition high-resolution tandem mass spectrometry. PPA analysis of albumin from nonsmoking women exposed to high levels of air pollution uncovered 68 unique location-specific modifications (LSMs) across 21 HSA residues. While nearly half were located at Cys34 (33 LSMs), 35 were detected on other residues, including Lys, His, Tyr, Ser, Met, and Arg. HSA adduct relative abundances spanned a ∼400 000-fold range and included putative products of exogenous (SO2, benzene, phycoerythrobilin) and endogenous (oxidation, lipid peroxidation, glycation, carbamylation) origin, as well as 24 modifications without annotations. PPA quantification revealed statistically significant changes in LSM levels across the 84 days of monitoring (∼3 HSA lifetimes) in the following putative adducts: Cys34 trioxidation, β-methylthiolation, benzaldehyde, and benzene diol epoxide; Met329 oxidation; Arg145 dioxidation; and unannotated Cys34 and His146 adducts. Notably, the PPA workflow can be extended to any protein. Pan-Protein Adductomics is a novel and powerful strategy for untargeted global exploration of protein modifications.
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