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Molecular changes to the rat renal cotransporters PEPT1 and PEPT2 due to ageing

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Abstract

Renal PEPT1 and PEPT2 cotransporters play an important role in the balance of circulating body oligopeptides and selected peptidomimetic drugs. We aim to comprehensively characterise age-related changes of the renal PEPT cotransporters at the gene, protein, and functional level. Brush border membrane vesicles (BBMV) and outer medulla membrane vesicles (OMMV) were isolated from the kidneys of young, middle-aged and old rats. The protein expression of PEPT1 was not only increased in BBMV from old rats, but PEPT1 also appeared in OMMV from middle-aged and old rats. SLC15A1 gene expression in the renal cortex increased in middle-aged group. PEPT2 protein expression was not only increased with ageing, but PEPT2 also was found in BBMV from middle-aged and old groups. SLC15A2 gene expression in the renal outer medulla increased in the old group. These changes in the expressions and localisations of PEPT1 and PEPT2 could explain the changes to transport activity in BBMV and OMMV. These findings provide novel insights that would be useful for maintaining protein nutrition and optimising the delivery of some peptidomimetic drugs in elderly individuals.

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Acknowledgements

We would like to thank Mr. Brian Cross and Mr. Jonathon Clay for their excellent technical assistance. This work was supported by University of New England (unnumbered grant), Australian Research Council (DP160102063) and University of Jeddah (Unnumbered Grant).

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Authors and Affiliations

  1. School of Science and Technology, University of New England, Armidale, NSW, 2351, Australia

    Othman A. Alghamdi, Nicholas M. Andronicos, Graham L. Jones & Pierre D. J. Moens

  2. School of Biomedical Sciences, University of Plymouth, Plymouth, PL4 8AA, UK

    Nicola King

  3. Discipline of Pathology, Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia

    Belal Chami & Paul K. Witting

  4. Department of Biological Sciences, Faculty of Science, Centre for Science and Medical Research, University of Jeddah, Jeddah, Saudi Arabia

    Othman A. Alghamdi

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  1. Othman A. Alghamdi
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Correspondence to Nicola King.

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Alghamdi, O.A., King, N., Andronicos, N.M. et al. Molecular changes to the rat renal cotransporters PEPT1 and PEPT2 due to ageing. Mol Cell Biochem 452, 71–82 (2019). https://doi.org/10.1007/s11010-018-3413-x

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