Trimethylamine-N-Oxide Treatment Induces Changes in the ATP-Binding Cassette Transporter A1 and Scavenger Receptor A1 in Murine Macrophage J774A.1 cells
Abstract
Background Recently, trimethylamine N-oxide was introduced as a risk factor for atherosclerosis in terms of helping foam cell formation and worsening atherosclerosis complications. The present study was performed to investigate whether/how trimethylamine N-oxide is involved in regulation of ATP-binding cassette transporter A1 and scavenger receptor A1 in macrophages at both mRNA and protein levels.Methods Murine macrophage J774A.1 cells were treated with micromolar concentrations of trimethylamine N-oxide and 4-phenylbutyric acid, a chemical chaperon, for different time intervals. Tunicamycin was also used as a control for induction of endoplasmic reticulum stress.Results Similar to tunicamycin, trimethylamine N-oxide increased scavenger receptor A1 in all treatment periods, whereas ATP-binding cassette transporter A1 was only reduced 24 h post-treatment with trimethylamine N-oxide at both mRNA and protein levels. In contrast, 4-phenylbutyric acid failed to induce such changes in either scavenger receptor A1 or ATP-binding cassette transporter A1.Conclusions The results of this study, in agreement with previous studies, confirm the mechanistic role of trimethylamine N-oxide in the upregulation of scavenger receptor A1, which potentially can promote its proatherogenic role. The results also showed downregulation of ATP-binding cassette transporter A1 in trimethylamine N-oxide treated macrophages which may indicate another possible proatherosclerotic mechanism for foam cell formation.
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High plasma TMAO levels are associated with risk for developing atherosclerosis.
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From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [16]
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Janeiro, M., Ramírez, M., Milagro, F., Martínez, J., & Solas, M. (2018) · Nutrients · doi:10.3390/nu10101398 · Cited by 631 · see citing works
- Authors
- Mohammadi, A., Najar, A. G., Yaghoobi, M. M., Jahani, Y., & Vahabzadeh, Z.
- Affiliations
- Kerman University of Medical Sciences (IR)
- Graduate University of Advanced Technology (IR)
- Corresponding author
- Vahabzadeh, Zakaria
- Venue
- Inflammation
- Published
- 2015-09-28
- Volume
- 39
- Issue
- 1
- Pages
- 393-404
- ISSN
- 0360-3997 (ISSN-L)
- 1573-2576
- OpenAlex
- W2236661062
- Cited by
- 53
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 14 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 2
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Inflammation (publishedVersion)
- PubMed (publishedVersion)
- Research Information System of Ardabil University of Medical Sciences (Ardabil University of Medical Sciences) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- trimethylamine N-oxide, ABCA1, macrophages, foam cell formation, atherosclerosis, 4-phenylbutyric acid, chemical chaperones, endoplasmic reticulum stress, tunicamycin, gene expression regulation
- MeSH terms
- Animals, Cell Line, Foam Cells, Macrophages, Methylamines, Phenylbutyrates, RNA, Messenger, Tunicamycin, Up-Regulation, Atherosclerosis, Scavenger Receptors, Class A, Mice, Endoplasmic Reticulum Stress, ATP Binding Cassette Transporter 1
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