Mohammadi Abbas, Najar Ahmad Gholamhoseynian, Yaghoobi Mohammad Mehdi, Jahani Yunes, Vahabzadeh Zakaria
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.
Inflammation. 2016 Feb;39(1):393-404. doi: 10.1007/s10753-015-0261-7.
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.
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.
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.
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.
最近，氧化三甲胺作为动脉粥样硬化的一个风险因素被提出，它有助于泡沫细胞形成并加重动脉粥样硬化并发症。本研究旨在调查氧化三甲胺是否以及如何在mRNA和蛋白质水平上参与巨噬细胞中ATP结合盒转运体A1和清道夫受体A1的调控。
用微摩尔浓度的氧化三甲胺和化学伴侣4-苯基丁酸处理小鼠巨噬细胞J774A.1细胞不同时间间隔。衣霉素也用作内质网应激诱导的对照。
与衣霉素相似，氧化三甲胺在所有处理时间段均增加清道夫受体A1，而ATP结合盒转运体A1仅在氧化三甲胺处理24小时后在mRNA和蛋白质水平均降低。相比之下，4-苯基丁酸未能诱导清道夫受体A1或ATP结合盒转运体A1发生此类变化。
本研究结果与先前研究一致，证实了氧化三甲胺在清道夫受体A1上调中的机制作用，这可能会促进其促动脉粥样硬化作用。结果还显示，氧化三甲胺处理的巨噬细胞中ATP结合盒转运体A1下调，这可能表明泡沫细胞形成的另一种可能的促动脉粥样硬化机制。
