title: 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.
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.|Endocrine and Metabolism Research Center, Institute of Basic and Clinical Physiology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ahmad Gholamhoseynian
authors.initials: AG
authors.lastname: Najar
authors.affiliation: Research Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Yaghoobi
authors.affiliation: 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.
authors.forename: Yunes
authors.initials: Y
authors.lastname: Jahani
authors.affiliation: Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. zakariav@yahoo.com.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Vahabzadeh
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005487:Foam Cells / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D010654:Phenylbutyrates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D064286:ATP Binding Cassette Transporter 1; D008744:Methylamines; D010654:Phenylbutyrates; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D014415:Tunicamycin; C577833:Abca1 protein, mouse; C495140:Msr1 protein, mouse; C075773:4-phenylbutyric acid; C005855:trimethyloxamine
keywords: ATP-binding cassette transporter 1; endoplasmic reticulum stress; macrophage; scavenger receptor class a; tunicamycin