Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors
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Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. / Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François.
in: AMINO ACIDS, Jahrgang 47, Nr. 4, 04.2015, S. 693-705.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors
AU - Vuille-dit-Bille, Raphael N
AU - Camargo, Simone M
AU - Emmenegger, Luca
AU - Sasse, Tom
AU - Kummer, Eva
AU - Jando, Julia
AU - Hamie, Qeumars M
AU - Meier, Chantal F
AU - Hunziker, Schirin
AU - Forras-Kaufmann, Zsofia
AU - Kuyumcu, Sena
AU - Fox, Mark
AU - Schwizer, Werner
AU - Fried, Michael
AU - Lindenmeyer, Maja
AU - Götze, Oliver
AU - Verrey, François
PY - 2015/4
Y1 - 2015/4
N2 - Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.
AB - Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.
KW - Amino Acid Transport Systems, Neutral
KW - Angiotensin-Converting Enzyme Inhibitors
KW - Animals
KW - Gene Expression
KW - Humans
KW - Intestinal Mucosa
KW - Intestines
KW - Membrane Transport Proteins
KW - Peptidyl-Dipeptidase A
KW - Protein Transport
KW - Up-Regulation
KW - Xenopus laevis
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00726-014-1889-6
DO - 10.1007/s00726-014-1889-6
M3 - SCORING: Journal article
C2 - 25534429
VL - 47
SP - 693
EP - 705
JO - AMINO ACIDS
JF - AMINO ACIDS
SN - 0939-4451
IS - 4
ER -