ArticleThe Journal of biological chemistry2012
p38 mitogen-activated protein kinase (MAPK) promotes cholesterol ester accumulation in macrophages through inhibition of macroautophagy.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- A noncanonical role for Jagged1 in endothelial mechanotransduction.The FEBS journal · 2026Article
- From Storage to Signaling: Lipid Droplet Lipolysis in Cholesterol Mobilization and Foam Cell Remodeling.Current atherosclerosis reports · 2026Review
- METTL16-mediated mJournal of experimental & clinical cancer research : CR · 2026Article
- Targeting p38 MAPK signaling pathway: Quercetin as a novel therapy for TMJ synovitis.International journal of molecular medicine · 2026Article
- Foam cells: tracing the diverse cellular origins and their linked signaling pathways.Journal of translational medicine · 2025Review
- The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway.Doklady. Biochemistry and biophysics · 2024Article
- Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33.Biomolecules · 2023Article
- A bibliometric analysis of autophagy in atherosclerosis from 2012 to 2021.Frontiers in pharmacology · 2022Article
- MAPK inhibitors protect against early‑stage osteoarthritis by activating autophagy.Molecular medicine reports · 2021Article
- AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway.Molecular cancer · 2021Article
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- Hydroxypyridinone-Coumarin Inhibits the Proliferation of MHCC97 and HepG2 Human Hepatocellular Carcinoma Cells and Down-Regulates the Phosphoinositide-3 Kinase Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Ginsenoside Compound K Attenuates Ox-LDL-Mediated Macrophage Inflammation and Foam Cell FormationFrontiers in pharmacology · 2020Article
- Lipid Droplets: A Significant but Understudied Contributor of Host⁻Bacterial Interactions.Cells · 2019Review
- Development of AD-Like Pathology in Skeletal Muscle.Journal of Parkinson's disease and Alzheimer's disease · 2019Article
- Overexpression of miR-223 inhibits foam cell formation by inducing autophagy in vascular smooth muscle cells.American journal of translational research · 2019Article
- Reactive Oxygen Species and p38MAPK Have a Role in the Smad2 Linker Region Phosphorylation Induced by TGF-β.Iranian journal of medical sciences · 2018Article
- PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and endothelial dysfunction.Journal of lipid research · 2018Article
- Inflammation-regulated mRNA stability and the progression of vascular inflammatory diseases.Clinical science (London, England : 1979) · 2017Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
p38 MAPK has been strongly implicated in the development of atherosclerosis, but its role in cholesterol ester accumulation in macrophages and formation of foam cells, an early step in the development of atherosclerosis, has not been investigated. We addressed this issue and made some brand new observations. First, elevated intracellular cholesterol level induced by the exposure to LDL-activated p38 MAPK and activation of p38 MAPK with anisomycin increased the ratio of cholesterol esters over free cholesterol, whereas inhibition of p38 MAPK with SB203580 or siRNA reduced the LDL loading-induced intracellular accumulation of free cholesterol and cholesterol esters in macrophages. Second, exposure to LDL cholesterol inhibited autophagy in macrophages, and inhibition of autophagy with 3-methyladenine increased intracellular accumulation of cholesterol (free cholesterol and cholesterol esters), whereas activation of autophagy with rapamycin decreased intracellular accumulation of free cholesterol and cholesterol esters induced by the exposure to LDL cholesterol. Third, LDL cholesterol loading-induced inhibition of autophagy was prevented by blockade of p38 MAPK with SB203580 or siRNA. Neutral cholesterol ester hydrolase was co-localized with autophagosomes. Finally, LDL cholesterol loading and p38 activation suppressed expression of the key autophagy gene, ulk1, in macrophages. Together, our results provide brand new insight about cholesterol ester accumulation in macrophages and foam cell formation.
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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.