Three-dimensional quantitative structure–activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1)

Thondorf, Iris; Voigt, Valerie; Schäfer, Sarah; Gebauer, Sebastian; Zebisch, Katja; Laug, Linda; Brandsch, Matthias

doi:10.1016/j.bmc.2011.08.058

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…18 out of a total of 41 potential metabolites were found to be associated either directly with PS or with PS associated disease. Interestingly, 16 of these 18 metabolites were reported to be up-regulated in diseased states [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53]. This was indicative of an increase in overall abundance of metabolites associated with stress as revealed in figure 3c.…”

Section: Discussionmentioning

confidence: 95%

Estimation of Psychological Stress in Humans: A Combination of Theory and Practice

2013

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Stress has long been known to increase susceptibility to health disorders. In 2009, American Psychological Association further established association of stress to serious health problems. However, a quantitative and accurate way to evaluate and estimate stress status of individuals is still a big challenge. It has been shown, in large animal models using cattle, that psychological stress can be quantified as well as disease susceptibility could be predicted through biomarker discovery. Taking cue from those studies, we have evaluated and estimated psychological stress level of individuals theoretically and validated experimentally. Various biomarkers have also been identified which can be associated to psychological stress to predict stress status of unknown individuals.

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Section: Discussionmentioning

confidence: 95%

Estimation of Psychological Stress in Humans: A Combination of Theory and Practice

2013

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“…One route for amino acid transport at the intestinal epithelial brush border is via PAT1, which is regulated by NHE3 maintenance of the H + electrochemical gradient across the membrane [20, 21]. The β-alanine can reportedly be transported by PAT1 across the intestinal epithelial brush border membrane.…”

Section: Discussionmentioning

confidence: 99%

“…At the intestinal enterocyte brush border, amino acids are transported through H + -coupled amino acid transporter 1 PAT1 ( SLC36A1) that symport H + and amino acids into the cells and maintain the dynamic H + electrochemical gradient [20, 21]. In particular, transport of both proline and alanine into intestinal cells has been shown to occur via the PAT1 [20, 22-24].…”

Section: Introductionmentioning

confidence: 99%

Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells

Shi

Zhao

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Dysfunctional autophagy has been reported to be associated with aberrant intestinal metabolism. Amino acids can regulate autophagic activity in intestinal epithelial cells (IECs). Na⁺/H⁺-exchanger 3 (NHE3) has been found to participate in the absorption of amino acids in the intestine, but whether NHE3 is involved in the regulation of autophagy in IECs is unclear. Methods: In the present study, an amino acid starvation-induced autophagic model was established. Then, the effects of alanine and proline with or without the NHE inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) were evaluated. Autophagy was examined based on the microtubule-associated light chain 3 (LC3) levels, transmission electron microscopy (TEM), tandem GFP-mCherry-LC3 construct, sequestosome-1 (SQSTM1, P62) mRNA and protein levels, and autophagy-related gene (ATG) 5, 7, and 12 expression levels. The autophagic flux was evaluated as the ratio of yellow (autophagosomes) to red (autolysosomes) LC3 puncta. Results: Following amino acid starvation, we found the LC3-II and ATG expression levels were enhanced in the IEC-18 cells. An increase in the number of autophagic vacuoles was concomitantly observed by TEM and confocal microscopy. Based on the results, supplementation with either alanine or proline depressed autophagy in the IEC-18 cells. Consistent with the elevated LC3-II levels, ATG expression increased upon NHE3 inhibition. Moreover, the mCherry-GFP-LC3 autophagic puncta representing both autophagosomes and autolysosomes per cell increased after EIPA treatment. Conclusions: These results demonstrate that NHE (most likely NHE3) may participate in the amino acid regulation of autophagy in IECs, which would aid in the design of better treatments for intestinal inflammation.

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“…[17,21,23,24,[26][27][28][29][30] We recently performed three-dimensional quantitative structure-activity relationship (3D QSAR) studies on~50 compounds that interact with hPAT1. [31] A pharmacophore model was used as a query for virtual screening to retrieve potential new substrates. Eleven compounds were identified as possible substrates of hPAT1, one of them indeed being arecaidine with a predicted apparent affinity constant (Ki) of 3 mm.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, arecoline, the methyl ester of arecaidine, was not able to inhibit H + -coupled l-[ 3 H]proline uptake (Ki > 35 mm). [31] Inhibition of the transport of a reference substrate into a cell does not necessarily mean that the competing compound itself is transported by the transporter in question. Such a compound could also represent a non-transported competitive or non-competitive inhibitor such as, for example, 5-hydroxy-l-tryptophan.…”

Section: Introductionmentioning

confidence: 99%

Transport of the areca nut alkaloid arecaidine by the human proton-coupled amino acid transporter 1 (hPAT1)

Voigt

Laug

Zebisch

et al. 2013

Journal of Pharmacy and Pharmacology

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Three-dimensional quantitative structure–activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1)

Cited by 12 publications

References 29 publications

Estimation of Psychological Stress in Humans: A Combination of Theory and Practice

Estimation of Psychological Stress in Humans: A Combination of Theory and Practice

Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells

Transport of the areca nut alkaloid arecaidine by the human proton-coupled amino acid transporter 1 (hPAT1)

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