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Segment-specific effects of resveratrol on porcine small intestinal dipeptide absorption depend on the mucosal pH and are due to different mechanisms: potential roles of different transport proteins and protein kinases.
The Journal of Nutritional Biochemistry ( IF 4.8 ) Pub Date : 2020-07-30 , DOI: 10.1016/j.jnutbio.2020.108467
Stefanie Klinger 1
Affiliation  

Numerous beneficial features of the polyphenol resveratrol (RSV) have been demonstrated in several tissues and cell culture models. There is also evidence, that RSV impairs intestinal nutrient transport but the underlying mechanisms are not understood. The aim of the present study was to evaluate whether RSV has also an impact on the H+-coupled transport of peptides via the peptide transporter 1 (PepT1) and to characterize RSV mediated changes in the apical abundance of nutrients transport proteins and protein kinases that may be involved.

RSV decreased the H+-coupled transport of peptides in the porcine small intestines in a pH and location specific manner (jejunum vs ileum) as measured in Ussing chamber experiments. The comparison of the effects of RSV with the effects of the cAMP/PKA-activating agent forskolin indicates that different mechanisms may be responsible in the intestinal segments. Additionally, it seems that the transport of peptides and glucose in the jejunum are inhibited via the same mechanism while there might be two mechanisms involved in the ileum.

Functional data and protein expression data indicate, that, besides PepT1, the activity of the Na+/H+-exchanger 3 (NHE3) may be involved. Protein kinase A (PKA) and AMP-activated kinase (AMPK) are both activated by RSV while the extracellular regulated kinase (ERK) and the serum and glucocorticoid induced kinase (SGK) are widely unaffected. Although PKA and AMPK are activated, AMPK seems not to be related to the effects of RSV. Additionally, both the functional data and the protein expression data reveal some interesting pH- and segment-specific differences.



中文翻译:

白藜芦醇对猪小肠二肽吸收的节段特异性作用取决于粘膜pH,并且归因于不同的机制:不同转运蛋白和蛋白激酶的潜在作用。

多酚白藜芦醇(RSV)的许多有益功能已在几种组织和细胞培养模型中得到证实。也有证据表明,RSV损害了肠道营养的运输,但其潜在机制尚不清楚。本研究的目的是评估RSV是否也对经由肽转运蛋白1(PepT1)的H +偶联的肽转运产生影响,并表征RSV介导的营养转运蛋白和蛋白激酶的顶端丰度变化可能涉及。

如在Ussing chamber实验中所测,RSV以pH和位置特定的方式(空肠vs回肠)降低了猪小肠中H +偶联的肽运输。RSV的作用与cAMP / PKA激活剂福司可林的作用的比较表明,肠段可能有不同的机制。另外,回肠中的肽和葡萄糖的运输似乎通过相同的机制被抑制而回肠中可能涉及两种机制。

功能数据和蛋白质表达数据表明,除了PepT1,还可能涉及Na + / H +-交换子3(NHE3)的活性。蛋白激酶A(PKA)和AMP激活激酶(AMPK)均被RSV激活,而细胞外调节激酶(ERK)以及血清和糖皮质激素诱导的激酶(SGK)则不受影响。尽管PKA和AMPK已激活,但AMPK似乎与RSV的影响无关。此外,功能数据和蛋白质表达数据都揭示了一些有趣的pH值和片段特异性差异。

更新日期:2020-07-30
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