Platelets Affect the Activity of Amino Acid Transporter SNAT4 in HuH-7 Human Hepatoma Cells.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-01-01 DOI:10.1248/bpb.b23-00904

Hitoshi Kashiwagi, Yuki Sato, Shunsuke Nashimoto, Shungo Imai, Yoh Takekuma, Mitsuru Sugawara

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Abstract

Platelets have been reported to exert diverse actions besides hemostasis and thrombus formation in the body. However, whether platelets affect transporter activity remains to be determined. In this study, we examined the effects of platelets on the activity of amino acid transporter system A, which is known to be changed by various factors, and we clarified the mechanism by which platelets affect system A activity. Among system A subtypes, we found that sodium-coupled neutral amino acid transporter (SNAT) 4 played a central role in the transport activity of system A in HuH-7 human hepatoma cells. Interestingly, platelets showed a biphasic effect on system A activity: activated platelet supernatants (APS) including the granule contents released from platelets downregulated system A activity at lower concentrations and the downregulation was suppressed at higher concentrations. The downregulation was due to a decrease in the affinity of SNAT4 for its substrate and not a decrease in the SNAT4 abundance on the plasma membrane. In addition, APS did not decrease the expression level of SNAT4 mRNA. On the other hand, platelets did not affect system A activity when the platelet suspension was added to HuH-7 cells. These results indicate that platelets indirectly affect the transport activity of system A by releasing bioactive substances but do not directly affect it by binding to HuH-7 cells.

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血小板影响 HuH-7 人肝癌细胞中氨基酸转运体 SNAT4 的活性

据报道，除了止血和血栓形成外，血小板还在体内发挥多种作用。然而，血小板是否会影响转运体的活性仍有待确定。本研究探讨了血小板对氨基酸转运体 A 系统活性的影响，并阐明了血小板影响 A 系统活性的机制。在 A 系统亚型中，我们发现钠偶联中性氨基酸转运体（SNAT）4 在 HuH-7 人肝癌细胞 A 系统转运活性中起着核心作用。有趣的是，血小板对系统 A 的活性有双相影响：活化血小板上清液（APS）（包括血小板释放的颗粒内容物）在较低浓度时会下调系统 A 的活性，而在较高浓度时这种下调被抑制。下调的原因是 SNAT4 对其底物的亲和力下降，而不是质膜上 SNAT4 丰度的下降。此外，APS 并未降低 SNAT4 mRNA 的表达水平。另一方面，当血小板悬浮液加入 HuH-7 细胞时，血小板并不影响 A 系统的活性。这些结果表明，血小板通过释放生物活性物质间接影响 A 系统的转运活性，但不会通过与 HuH-7 细胞结合直接影响 A 系统的转运活性。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.