ArticleThe Journal of biological chemistry2015
Lipopolysaccharides Promote S-Nitrosylation and Proteasomal Degradation of Liver Kinase B1 (LKB1) in Macrophages in Vivo.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Myeloid liver kinase B1 contributes to lung inflammation induced by lipoteichoic acid but not by viable Streptococcus pneumoniae.Respiratory research · 2022Article
- Lipopolysaccharide Accelerates Neuropilin-1 Protein Degradation by Activating the Large GTPase Dynamin-1 in Macrophages.Inflammation · 2022Article
- Review
- Critical Role of Lkb1 in the Maintenance of Alveolar Macrophage Self-Renewal and Immune Homeostasis.Frontiers in immunology · 2021Article
- Regulation of cytochrome P450 enzyme activity and expression by nitric oxide in the context of inflammatory disease.Drug metabolism reviews · 2020Review
- Tyrosine Nitration Contributes to Nitric Oxide-Stimulated Degradation of CYP2B6.Molecular pharmacology · 2020Article
- Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma.Scientific reports · 2018Article
- Review
- Liver Kinase B1 Links Macrophage Metabolism Sensing and Atherosclerosis.Circulation research · 2017Article
- Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis.Circulation research · 2017Article
- Nitric oxide-regulated proteolysis of human CYP2B6 via the ubiquitin-proteasome system.Free radical biology & medicine · 2017Article
- A novel role for myeloid cell-specific neuropilin 1 in mitigating sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- [Role of interleukin-17 in alveolar fluid clearance in mice with acute lung injury].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
LKB1 (liver kinase B1) plays important roles in tumor suppression, energy metabolism, and, recently, in innate immune responses. However, how LKB1 is regulated under physiological or pathological conditions is still unclear. Here, we report that LKB1 protein (but not mRNA) was decreased in both LPS-treated RAW 264.7 cells and peritoneal macrophages isolated from LPS-challenged mice. Additional LPS treatment promoted protein ubiquitination and degradation of LKB1. Pharmacological inhibition or gene silencing of inducible NOS abrogated LPS-induced LKB1 degradation, whereas exposure of RAW 264.7 cells to S-nitroso-l-glutathione, a NO donor, triggered LKB1 S-nitrosylation. Consistently, mutation of one cysteine (C430S) in LKB1 prevented LPS-induced S-nitrosylation, ubiquitination, and degradation. Moreover, S-nitrosylation and ubiquitination of LKB1 were confirmed in macrophages from LPS-challenged mice in vivo. Co-administration of the inducible NOS inhibitor S-methylisothiourea or the proteasome inhibitor MG132 prevented LPS-induced LKB1 degradation and improved the survival rate. Finally, mice lacking LKB1 in macrophages had significantly lower survival rates in response to LPS challenge compared with wild-type mice. Thus, we concluded that LKB1 is degraded by LPS treatment via S-nitrosylation-dependent proteasome pathways, and this had a protective role in LPS-induced septic shock.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.