Abbas Mohammadi1,2, Ahmad Gholamhoseynian Najar1, Mohammad Mehdi Yaghoobi3, Yunes Jahani4, Zakaria Vahabzadeh5. 1. Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 2. Endocrine and Metabolism Research Center, Institute of Basic and Clinical Physiology, Kerman University of Medical Sciences, Kerman, Iran. 3. Research Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran. 4. Social Determinants of Health Research Center, Institute of Futures Studies in Health, Department of Biostatistics and Epidemiology, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran. 5. Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. zakariav@yahoo.com.
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.
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.
Authors: Hon Jen Wong; Wen Hui Lim; Cheng Han Ng; Darren Jun Hao Tan; Glenn K Bonney; Alfred W C Kow; Daniel Q Huang; Mohammad Shadab Siddiqui; Mazen Noureddin; Nicholas Syn; Mark D Muthiah Journal: Front Med (Lausanne) Date: 2022-05-10
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