Journal article
Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells
Toxicology and applied pharmacology, Vol.449, pp.116110-116110
08/15/2022
DOI: 10.1016/j.taap.2022.116110
PMID: 35688186
Abstract
Protein phosphorylation is the most common type of post-translational modification where serine, threonine or tyrosine are reversibly bound to the phosphate group of ATP in a reaction catalyzed by protein kinases. Phosphorylation plays an important role in regulation of cell homeostasis, including but not limited to signal perception and transduction, gene expression and function of proteins. Protein phosphorylation happens on a fast time scale and represents an energy-efficient way for the cell to adapt to exposure to chemical stressors. To understand the cascade of cellular signaling induced by exposure to chemicals, we have exposed HepG2 cells to three chemicals with different modes of action, namely, caffeine, coumarin, and quercetin in a concentration and time response manner. Significantly upregulated and downregulated phosphosites were screened to analyze the activation/deactivation of signaling pathways by protein kinases. In total, 69, 44 and 12 signaling pathways were found enriched in caffeine, coumarin and quercetin treated cells, respectively, of which 9 pathways were co-enriched with 11 jointly responded kinases. Among identified co-responded kinases, CDK1, MAPK1 and MAPK3 play important roles in cell cycle and insulin signaling pathways. Quantitative phosphoproteomics can sensitively distinguish the effects of different chemicals on cells, allowing the assessment of chemical safety through changes in substrates and metabolic pathways at the cellular level, which is important for the development of non-animal approaches for chemical safety assessment.
•Phosphorylation of protein substrates were found to be changed by treatment of low-dose of chemicals.•Caffeine, coumarin and quercetin induce a series of co-responded kinases with quite different phosphorylated substrate profiles.•Three chemicals disturb the cell cycle and insulin signaling pathways by affecting different protein substrates.
Details
- Title: Subtitle
- Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells
- Creators
- Zhenpeng Zhang - Protein SciencesYao Zhang - Beijing Proteome Research CenterYuan Li - Beijing Proteome Research CenterSonghao Jiang - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, ChinaFeng Xu - Beijing Proteome Research CenterKaixuan Li - Beijing Proteome Research CenterLei Chang - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, ChinaHuiying Gao - Beijing Institute of Radiation Medicine, Beijing 100039, ChinaPredrag Kukic - Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ, UKPaul Lawford Carmichael - Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ, UKMark Liddell - Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ, UKJin LiQiang Zhang - Emory UniversityZhitang Lyu - Hebei Province Key Lab of Research and Application on Microbial Diversity, College of Life Sciences, Hebei University, Baoding 071002, ChinaShuangqing Peng - Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, ChinaTao Zuo - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, ChinaLiz Tulum - Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ, UKPing Xu - State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.449, pp.116110-116110
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.taap.2022.116110
- PMID
- 35688186
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Language
- English
- Date published
- 08/15/2022
- Academic Unit
- Neurology
- Record Identifier
- 9984302209502771
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