Phosphoproteomics and Proteomics Reveal Metabolism as a Key Node in LPS-Induced Acute Inflammation in RAW264.7
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ORIGINAL ARTICLE
Phosphoproteomics and Proteomics Reveal Metabolism as a Key Node in LPS-Induced Acute Inflammation in RAW264.7 Yu Luo ,1 Qing Jiang,1 Zhengwen Zhu,1 Haseeb Sattar,2 Jiasi Wu,1 Wenge Huang,1 Siyu Su,1 Yusheng Liang,1 Ping Wang,1,3 and Xianli Meng1,3
Abstract—To better understand the acute inflammatory mechanisms, the modulation, and
to investigate the key node in predicting inflammatory diseases, high-sensitivity LC-MS/ MS-based proteomics and phosphoproteomics approaches were used to identify differential proteins in RAW264.7 macrophages with lipopolysaccharide (LPS). Furthermore, differential proteins and their main biological process, as well as signaling pathways, were analyzed through bioinformatics techniques. The biological process comparison revealed 219 differential proteins and 405 differential phosphorylation proteins, including major regulatory factors of metabolism (PFKL, PGK1, GYS1, ACC, HSL, LDHA, RAB14, PRKAA1), inflammatory signaling transduction (IKKs, NF-κB, IRAK, IKBkb, PI3K, AKT), and apoptosis (MCL-1, BID, NOXA, SQSTM1). Label-free proteome demonstrated canonical inflammation signaling pathways such as the TNF signaling pathway, NF-κB signaling pathway, and NOD-like receptor signaling pathway. Meanwhile, phosphoproteome revealed new areas of acute inflammation. Phosphoproteomics profiled that glycolysis was enhanced and lipid synthesis was increased. Overall, the AMPK signaling pathway is the key regulatory part in macrophages. These revealed that the early initiation phase of acute inflammation primarily regulated the phosphoproteins of glucose metabolic pathway and lipid synthesis to generate energy and molecules, along with the enhancement of pro-inflammatory factors, and further induced apoptosis. Phosphoproteomics provides new evidence for a complex network of specific but synergistically acting mechanisms confirming that metabolism has a key role in acute inflammation. KEY WORDS: phosphoproteomics; proteomics; acute inflammation; metabolism.
1
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China 2 International School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China 3 To whom correspondence should be addressed at College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China. E-mails: [email protected]; [email protected]
INTRODUCTION Inflammation is an essential immune response after tissue injury involving various inflammatory factors. It is a common and important basic pathological process that is associated with numerous diseases [1]. Acute inflammation is the initial immune response of the body to harmful stimuli [2]. At the early stage of the immune response,
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Luo, Jiang, Zhu, Sattar, Wu, Huang, Su, Liang, Wang, and Meng acute inflammation promotes tissue repair and helps to
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