A mass spectrometry-based strategy combined with bioinformatics: A simple preclinical model for profiling valproic-acid-induced major proteins and modifications in human liver cells. (July 2017)

• Record Type: Journal Article
• Authors: Wu, Chun-Yi; Hsieh, Tusty-Jiuan; Tseng, Wei-Lung; Keng, Chun-Lan; Lu, Chi-Yu
• Is Part Of: Process biochemistry. Volume 58(2017)
• Page Start: 78
• Page End: 84
• Publication Date: 2017-07
• Subjects: Valproic acid -- Hepatotoxicity -- Reactive oxygen species -- Indicator; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2017.04.021
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Highlights: The valproic acid (VA) induced protein profiles and modifications were identified by nanoUPLC-LTQ Orbitrap. Most abundant proteins were cytoplasmic and nuclear proteins after VA treatment. Oxidation was the most common modification observed in cells treated with VA. Unique amino acid modifications in proteins are good indicators of oxidative stress. Abstract: The clinical use of valproic acid (VA) as an antiepileptic drug is associated with adverse effects such as hepatotoxicity and encephalopathy. These potential complications may be caused by reactive oxygen species (ROS) produced during the metabolic processing of VA. In this study, we used screening to identify cellular protein markers of VA-induced oxidative stress in human liver cells. To confirm that the protein modifications were induced by VA, nano-ultra-performance liquid chromatography (nanoUPLC) coupled with tandem mass spectrometry (MS/MS) was used for structural identification. Protein modifications induced by oxidative stress were found to involve crotonaldehyde, 4-hydroxynonenal, an oxygen atom, nitric oxide, and the nitro and acetyl groups. The data on the above-mentioned protein modifications may serve as indicators of apoptosis, oxidative stress, or other adverse reactions induced by the clinical use of VA.