Plasma Proteome Dynamics: Analysis of Lipoproteins and Acute Phase Response Proteins with 2H2O Metabolic Labeling

Li, Ling; Willard, Belinda; Rachdaoui, Nadia; Kirwan, John P.; Sadygov, Rovshan G.; Stanley, William C.; Previs, Stephen F.; McCullough, Arthur J.; Kasumov, Takhar

doi:10.1074/mcp.m111.014209

Cited by 38 publications

(64 citation statements)

References 52 publications

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“…In animal models, body 2 H 2 O enrichments can be 3.0-8.0% Klionsky et al, 2012;Li et al, 2012;Price, Holmes, et al, 2012;Price, Khambatta, et al, 2012). Examples of body water labeling protocols in humans are described in Fig.…”

Section: Constraints On 2 H 2 O Administration and Factors To Considementioning

confidence: 98%

“…There are potential applications of isotope analyses of daughter ions, such as immonium ions from amino acids, in MS/MS mode using ion traps (T. Angel, unpublished observations). We have found that TOF instruments operated in MS-only mode provide sufficient isotope accuracy and precision required to detect subtle changes in peptide isotopomer distributions achieved through body water enrichments of 1-5% Decaris et al, 2014;Klionsky et al, 2012;Li et al, 2012;Price, Holmes, et al, 2012;Price, Khambatta, et al, 2012).…”

Section: Ms Instrumentationmentioning

confidence: 98%

“…These quantitative proteomics approaches are often applied in cross-sectional studies capturing a snapshot of relative protein abundance profiles, but do not directly capture the dynamics of the biologic system. Incorporation of metabolic labeling with stable isotopes in vivo allows for the measurement of biological transients or flux, providing insights into the essential dynamic properties of a living system (Claydon & 2012; Klionsky et al, 2012;Li et al, 2012;Price, Holmes, et al, 2012;Price, Khambatta, et al, 2012).…”

Section: Dynamic Proteomicsmentioning

confidence: 99%

“…Heavy water ( 2 H 2 O) applications are ideal and almost universally applicable for combinatorial analysis of the major classes of biological polymers, including proteins (Busch et al, 2006;Klionsky et al, 2012;Li et al, 2012;Price, Holmes, et al, 2012;Price, Khambatta, et al, 2012). Heavy water applications bring many practical advantages:…”

Section: Advantages Of the Combinatorial Analysis (Mida) Approach Formentioning

confidence: 99%

“…The synthesis, breakdown, transport, secretion, and storage of proteins had not been readily directly measurable, however, through traditional proteomic techniques. The combination of metabolic labeling with stable isotopes and MS-based proteomics constitutes a powerful pairing of approaches for the unbiased interrogation of proteome-wide protein dynamics in complex biological systems Claydon, Thom, Hurst, & Beynon, 2012;Klionsky et al, 2012;Li et al, 2012;Price, Holmes, et al, 2012;Price, Khambatta, et al, 2012).…”

Section: Tools For Measuring Fluxes Differ From Tools For Measuring Smentioning

confidence: 99%

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Dynamic Proteomics

Holmes

Angel

et al. 2015

Methods in Enzymology

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Section: Constraints On 2 H 2 O Administration and Factors To Considementioning

confidence: 98%

Section: Ms Instrumentationmentioning

confidence: 98%

Section: Dynamic Proteomicsmentioning

confidence: 99%

Section: Advantages Of the Combinatorial Analysis (Mida) Approach Formentioning

confidence: 99%

Section: Tools For Measuring Fluxes Differ From Tools For Measuring Smentioning

confidence: 99%

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Dynamic Proteomics

Holmes

Angel

et al. 2015

Methods in Enzymology

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Measurement of protein in vivo turnover rate with metabolic labeling using LC–MS

Shi

Weng

Jian

2023

Biomedical Chromatography

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Understanding the protein dynamics of a drug target is important for pharmaceutical research because it provides insight into drug design, target engagement, pharmacodynamics and drug efficacy. Nonradioactive isotope labeling has been the method of choice for protein turnover measurement thanks to the advancement of high‐resolution mass spectrometry. While the changes in proteome in cell cultures can be monitored precisely, as the culture media can be completely replaced with 2H‐, 15N‐ or 13C‐labeled essential amino acids, quantifying rates of protein synthesis in vivo is more challenging. The amount of isotope tracer that can be administered into the body is relatively small compared with the existing protein, thus requiring more sensitive detection, and the precursor‐product labeling relationship is more complicated to interpret. The purpose of this review is to provide an overview of the principles of in vivo protein turnover studies using deuterium water (2H2O) with an emphasis on targeted protein analysis by hybrid LC–MS assay platforms. The pursuit of these opportunities will facilitate drug discovery and research in preclinical and clinical stages.

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Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

Wilkinson

2016

Mass Spectrometry Reviews

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Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13C), nitrogen (15N), oxygen (18O), and hydrogen (2H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to “trace” the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC‐MS to LC‐MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level. Importantly, it will detail how this development has been closely aligned to the technological development within the area of mass spectrometry. Without the dedicated development provided by these mass spectrometrists over the past century, the use of stable isotope tracers within the field of protein metabolism would not be as widely applied as it is today, this relationship will no doubt continue to flourish in the future and stable isotope tracers will maintain their importance as a tool within the biological sciences for many years to come. © 2016 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Mass Spec Rev

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Plasma Proteome Dynamics: Analysis of Lipoproteins and Acute Phase Response Proteins with 2H2O Metabolic Labeling

Cited by 38 publications

References 52 publications

Dynamic Proteomics

Dynamic Proteomics

Measurement of protein in vivo turnover rate with metabolic labeling using LC–MS

Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

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