Abstract
Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS).Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot.Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot.Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.
Highlights
Seizures are the presenting signs of patients with glioma and contribute to low quality of life [1, 2]
The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, tricarboxylic acid (TCA) cycle, and necroptosis
Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot
Summary
Seizures are the presenting signs of patients with glioma and contribute to low quality of life [1, 2]. Antiseizure medication (ASM) administration is recommended in patients with glioma-associated seizures (GAS). Lysine acetylation of proteins has recently been considered as a highly conserved post-translational modification (PTM) that regulates numerous enzymes of metabolic process in mitochondria, including tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and metabolism of amino acids and fatty acid [3,4,5]. Lysine acetylation is managed by deacetylases and acetyltransferases, which plays a key role in biological processes for signal transduction and cellular metabolism [8]. Recent studies indicate that abnormal deacetylase and acetyltransferase expressions are associated with the tumorigenesis and progression of glioma [9,10,11]. The role of lysine acetylation in glioma with seizures remains unknown
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