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Effect of ageing and hypertension on the expression and activity of PEPT2 in normal and hypertrophic hearts
Amino Acids ( IF 3.0 ) Pub Date : 2021-01-06 , DOI: 10.1007/s00726-020-02936-y
Othman Alghamdi 1 , Nicola King 2 , Graham L Jones 3 , Pierre D J Moens 3
Affiliation  

Some dipeptides have been implicated in myocardial protection, but little is known about their membrane transporter PEPT2. The aim of this study was to determine whether the expression and activity of the cardiac-type PEPT2 cotransporter could be affected by ageing and/or hypertension. Sarcolemmal vesicles (SV) were isolated from the hearts of all rat groups using a standard procedure to investigate the transport activity and protein abundance by fluorescence spectroscopy and Western blot, respectively. SLC15A2 “PEPT2” gene expression was relatively quantified by RT-qPCR. In the Wistar rat groups, the protein and gene expression of PEPT2 were upregulated with ageing. These changes were accompanied by corresponding increases in the competitive inhibition and the transport rate (Vmax) of β-Ala-Lys (AMCA) into SV isolated from middle-aged hearts. Although, the transport rate of β-Ala-Lys (AMCA) into SV isolated from old hearts was significantly the lowest compared to middle-aged and young adult hearts, the inhibition percentage of β-Ala-Lys (AMCA) transport by Gly-Gln was the highest. In the WKY and SHR rat groups, Y-SHR hypertrophied hearts showed an increase in PEPT2 gene expression accompanied by a significant decrease in protein expression and activity. With advanced age, however, M-SHR hypertrophied hearts revealed significantly lower gene expression, but higher protein expression and activity than Y-SHR hearts. These findings suggest that increased expression of PEPT2 cotransporter in all types of middle-aged hearts could be exploited to facilitate di-and tripeptide transport by PEPT2 in these hearts, which subsequently could result in improved myocardial protection in these populations.



中文翻译:

衰老和高血压对正常和肥厚心脏 PEPT2 表达和活性的影响

一些二肽与心肌保护有关,但对其膜转运蛋白 PEPT2 知之甚少。本研究的目的是确定心脏型 PEPT2 协同转运蛋白的表达和活性是否会受到衰老和/或高血压的影响。使用标准程序从所有大鼠组的心脏中分离肌膜囊泡 (SV),分别通过荧光光谱和蛋白质印迹研究转运活性和蛋白质丰度。SLC15A2“PEPT2”基因表达通过RT-qPCR相对定量。在 Wistar 大鼠组中,PEPT2 的蛋白质和基因表达随着年龄的增长而上调。这些变化伴随着竞争抑制和转运速率(V max) 的 β-Ala-Lys (AMCA) 转化为从中年心脏分离的 SV。尽管与中青年心脏相比,β-Ala-Lys (AMCA) 向 SV 的转运率显着最低,但 Gly-对 β-Ala-Lys (AMCA) 转运的抑制百分比Gln 是最高的。在 WKY 和 SHR 大鼠组中,Y-SHR 肥大心脏显示 PEPT2 基因表达增加,伴随着蛋白质表达和活性的显着降低。然而,随着年龄的增长,M-SHR 肥大的心脏显示出比 Y-SHR 心脏显着降低的基因表达,但更高的蛋白质表达和活性。这些发现表明,在所有类型的中年心脏中,PEPT2 协同转运蛋白的表达增加可用于促进 PEPT2 在这些心脏中的二肽和三肽转运,

更新日期:2021-01-06
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