{"doi":"10.1073/pnas.012432399","title":"Tumor necrosis factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of a specific methylglyoxal-derived AGE","abstract":"<jats:p>Tumor necrosis factor (TNF)-induced cell death in the fibrosarcoma cell line L929 is a caspase-independent process that is characterized by increased production of reactive oxygen species (ROS) in the mitochondria. To elucidate this ROS-dependent cell death pathway, a comparative study of the phosphoproteins present in TNF-treated and control cells was performed. Here we report that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death. We also show that TNF induces a substantial increase in intracellular levels of methylglyoxal (MG) that leads to the formation of a specific MG-derived advanced glycation end product and that this formation occurs as a consequence of increased ROS production. These data indicate that MG modification of proteins is a targeted process and that MG may thus function as a signal molecule during the regulation of cell death. Furthermore, we provide evidence that the TNF-induced phosphorylation of glyoxalase I is not involved in detoxification of MG by means of the glyoxalase system, but that phosphorylated glyoxalase I is on the pathway leading to the formation of a specific MG-derived advanced glycation end product.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2002,"id":672199,"datarank":0.692268077526189,"base_score":4.61512051684126,"endowment":4.61512051684126,"self_citation_contribution":0.692268077526189,"citation_network_contribution":0.0,"self_endowment_contribution":0.692268077526189,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":100,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1312916,"name":"Jianqiang Mao","orcid":null,"position":1,"is_corresponding":false},{"id":1756228,"name":"Frank W. 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To elucidate this ROS-dependent cell death pathway, a comparative study of the phosphoproteins present in TNF-treated and control cells was performed. Here we report that TNF induces an increased phosphorylation of glyoxalase I that is mediated by protein kinase A and required for cell death. We also show that TNF induces a substantial increase in intracellular levels of methylglyoxal (MG) that leads to the formation of a specific MG-derived advanced glycation end product and that this formation occurs as a consequence of increased ROS production. These data indicate that MG modification of proteins is a targeted process and that MG may thus function as a signal molecule during the regulation of cell death. Furthermore, we provide evidence that the TNF-induced phosphorylation of glyoxalase I is not involved in detoxification of MG by means of the glyoxalase system, but that phosphorylated glyoxalase I is on the pathway leading to the formation of a specific MG-derived advanced glycation end product.</jats:p>","is_dataset_classified":null,"base_score":4.61512051684126,"endowment":4.61512051684126,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11792832","pmcid":"PMC117411","openalex_id":"https://openalex.org/W2115652492","authors":[],"funders":[],"total_grants":0,"fwci":3.6847,"citation_percentile":0.9317639,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":5},{"year":2014,"count":7},{"year":2015,"count":3},{"year":2016,"count":3},{"year":2017,"count":5},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":5},{"year":2021,"count":2},{"year":2022,"count":4},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":2}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.012432399","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.012432399","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11792832","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/117411","host_type":"repository"},{"url":"http://hdl.handle.net/1854/LU-156370","host_type":"repository"}],"fields_of_study":["Advanced Glycation End Products research","Alcohol Consumption and Health Effects","S100 Proteins and Annexins","Animals","Cell Death","Cyclic AMP-Dependent Protein Kinases","Glycation End Products, Advanced","Lactoylglutathione Lyase","Mice","Phosphorylation","Pyruvaldehyde","Reactive Oxygen Species","Tumor Cells, Cultured","Tumor Necrosis Factor-alpha"],"mesh_terms":["Animals","Lactoylglutathione Lyase","Phosphorylation","Pyruvaldehyde","Tumor Cells, Cultured","Tumor Necrosis Factor-alpha","Cell Death","Glycation End Products, Advanced","Reactive Oxygen Species","Cyclic AMP-Dependent Protein Kinases","Mice"],"keywords":["Methylglyoxal","Lactoylglutathione lyase","Programmed cell death","Advanced glycation end-product","Phosphorylation","Glycation","Cell biology","Reactive oxygen species","Chemistry","Tumor necrosis factor alpha","Intracellular","Biochemistry","Apoptosis","Biology","Endocrinology","Enzyme","Receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T08:02:43.909978Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}