Dyslipidemia and hyperglycemia induce overexpression of Syndecan-3 in erythrocytes and modulate erythrocyte adhesion.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Smitha Honnalagere Mallanna, Rajesh K Thimmulappa, Nandini D Chilkunda
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引用次数: 0

Abstract

Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g. hyperglycemia or hypercholesterolemia) increase erythrocyte adhesion to various extracellular matrix components, potentially through altering glycosaminoglycans (GAGs). In this study, we have investigated the expression of syndecan (Sdc) family members that could be involved in mediating cytoadherence under conditions of dyslipidemia and hyperglycemia. Among the Sdc family members analysed, we found significant overexpression of Sdc-3 in erythrocyte membranes harvested from high-fat-fed control and diabetic animals. Animal studies revealed a positive correlation between Sdc-3 expression, blood sugar levels and erythrocyte adhesion. In the human study, diabetic cohorts with body mass index >24.9 showed significantly increased expression of Sdc-3. Interestingly, blocking the Sdc-3 moiety with an anti-Sdc-3 antibody revealed that the core protein might not be directly involved in erythrocyte adhesion to fibronectin despite the GAGs bringing about adhesion. Lastly, Nano liquid chromatography-mass spectrometry/MS verified the presence of Sdc-3 in erythrocyte membranes. In conclusion, the high-fat diet and diabetes modulated Sdc-3 expression in the erythrocyte membrane, which may alter its adhesive properties and promote vascular complications.

血脂异常和高血糖会诱导红细胞中的Syndecan-3过度表达,并调节红细胞的粘附性。
红细胞是血管的重要组成部分,除携带氧气外,还在维持血管稳态方面发挥着重要作用。此前,我们曾报道过,体内环境的变化(如高血糖或高胆固醇血症)会增加红细胞对各种 ECM 成分的粘附,这可能是通过改变糖胺聚糖(GAGs)实现的。在本研究中,我们调查了在血脂异常和高血糖条件下可能参与介导细胞粘附的辛迪加(Sdc)家族成员的表达情况。在分析的 Sdc 家族成员中,我们发现 Sdc-3 在高脂饮食对照组和糖尿病动物收获的红细胞膜中显著过表达。动物研究显示,Sdc-3 的表达、血糖水平和红细胞粘附性之间存在正相关。在人体研究中,体重指数大于 24.9 的糖尿病组群显示 Sdc-3 的表达明显增加。有趣的是,用抗 Sdc-3 抗体阻断 Sdc-3 分子后发现,尽管 GAGs 带来了粘附力,但核心蛋白可能并不直接参与红细胞与纤维粘连蛋白的粘附。最后,纳米 LC-MS/MS 验证了 Sdc-3 存在于红细胞膜中。总之,高脂饮食和糖尿病调节了红细胞膜中Sdc-3的表达,这可能会改变红细胞膜的粘附性,促进血管并发症的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of biochemistry
Journal of biochemistry 生物-生化与分子生物学
CiteScore
4.80
自引率
3.70%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.
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