Epidermal growth factor (EGF) increases the renal amino acid transport capacity in amino acid loaded rats

Fleck, Christian; Pertsch, J.

doi:10.1007/bf01320896

Cited by 4 publications

(1 citation statement)

References 45 publications

(41 reference statements)

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“…Epidermal growth factor (EGF) plays a number of key roles in the kidney, contributing to cellular proliferative and survival pathways, renal metabolism [1], regenerative hyperplasia [2], tubulointerstitial injury [3], tubulogenesis [4], transport [5], renal cyst formation [6] and renal development [7]. EGF also has been implicated in the genesis and development of polycystic kidney disease [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor activates Na+/H+ exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin

Coaxum

Garnovskaya

Göõz

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Sodium-proton exchanger type 1 (NHE-1) is ubiquitously expressed, is activated by numerous growth factors, and plays significant roles in regulating intracellular pH and cellular volume, proliferation and cytoskeleton. Despite its importance, little is known about its regulation in renal glomerular podocytes. In the current work, we studied the regulation of NHE-1 activity by the epidermal growth factor receptor (EGFR) in cultured podocytes. RT-PCR demonstrated mRNAs for NHE-1 and NHE-2 in differentiated podocytes, as well as for EGFR subunits EGFR/ErbB1, Erb3, and ErbB4. EGF induced concentration-dependent increases in proton efflux in renal podocytes as assessed using a Cytosensor microphysiometer, were diminished in the presence of 5-(N-methyl-N-isobutyl) amiloride or in a sodium-free solution. Furthermore, pharmacological inhibitors of janus kinase (Jak2) and calmodulin (CaM) attenuated EGF-induced NHE-1 activity. Co-immunoprecipitation studies determined that EGF induced formation of complexes between Jak2 and CaM, as well as between CaM and NHE-1. In addition, EGF increased levels of tyrosine phosphorylation of Jak2 and CaM. The EGFR kinase inhibitor, AG1478, blocked activation of NHE-1, but did not block EGF-induced phosphorylation of Jak2 or CaM. These results suggest that EGF induces NHE-1 activity in podocytes through two pathways: (1) EGF → EGFR → Jak2 activation (independent of EGFR tyrosine kinase activity) → tyrosine phosphorylation of CaM → CaM binding to NHE-1 → conformational change of NHE-1 → activation of NHE-1; and (2) EGF →EGFR → EGFR kinase activation → association of CaM with NHE-1 (independent of Jak2) → conformational change of NHE-1 → activation of NHE-1.

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Section: Introductionmentioning

confidence: 99%

Epidermal growth factor activates Na+/H+ exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin

Coaxum

Garnovskaya

Göõz

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Regulation of renal amino acid (AA) transport by hormones, drugs and xenobiotics - a review

2003

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Major advances have recently been made in our understanding of the mechanisms and functions of amino acid transport in mammalian cells: - from the whole organism to transporter molecular structure. In this article, we present a brief overview of current knowledge concerning amino acid transporters, followed by a detailed discussion of the relevance of this new information to our broader understanding of the physiological regulation of amino acid handling in the kidney. We focus especially on the influence of hormones and xenobiotics on renal amino acid transport systems. In a growing number of cases, it now seems possible to correlate the effects of hormones, drugs, and xenobiotics with the capacity of renal amino acid transporters. This topic is of clinical relevance for the treatment of many amino acid reabsorption disorders. For example, under suitable conditions glucocorticoids and thyroid hormones stimulate renal reabsorption of amino acids and might therefore be of benefit in the treatment of different kinds of aminoaciduria. Hormonal regulation also underlies the postnatal development of renal amino acid reabsorption capacity, which can be stimulated to mature earlier after exogenous administration of e.g. glucocorticoids. In contrast, many compounds (e.g. heavy metal complexes) selectively damage renal amino acid transporters resulting in urinary amino acid loss. These types of phenomena (stimulation or inhibition of amino acid transporters in the kidney) are reviewed from the perspectives of our new molecular understanding of transport processes and of clinical relevance.

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Identification of the site of glucocorticoid action on neutral amino acid transport in superficial nephrons of rat kidney

2000

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Glucocorticoid hormones enhance the reabsorptive capacity of filtered amino acids in rat kidney, as it was shown in previous in vivo clearance experiments. In the present study, the site of glucocorticoid action on neutral amino acid transport in superficial nephrons of rat kidney was investigated using in vivo micropuncture technique. Adult female Wistar rats were treated with dexamethasone (DEX), and fractional excretion of L-glutamine (L-Gln) and L-leucine (L-Leu) were determined and related to inulin after microinfusion into different nephron segments. DEX reduced fractional excretion of both neutral amino acids as a sign of enhanced reabsorptive capacity. The site of main DEX action on L-Leu reabsorption has been localized in the proximal straight tubule. However, in the case of L-Gln, the inhibition of gamma-glutamyltranspeptidase (gamma-GT) by administration of acivicin indicated the importance of this brush border enzyme in reduced L-Gln excretion. DEX enhanced gamma-GT activity by tubular acidification. It can be presumed a DEX-inducible transport system for neutral amino acids mainly localized in proximal straight tubules of rat kidney.

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Epidermal growth factor (EGF) increases the renal amino acid transport capacity in amino acid loaded rats

Cited by 4 publications

References 45 publications

Epidermal growth factor activates Na+/H+ exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin

Epidermal growth factor activates Na+/H+ exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin

Regulation of renal amino acid (AA) transport by hormones, drugs and xenobiotics - a review

Identification of the site of glucocorticoid action on neutral amino acid transport in superficial nephrons of rat kidney

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