Abstract:Basolateral efflux is a necessary step in transepithelial (re)absorption of amino acids from small intestine and kidney proximal tubule. The best characterized basolateral amino acid transporters are y+LAT1-4F2hc and LAT2-4F2hc that function as obligatory exchangers and thus, do not contribute to net amino acid (re)absorption. The aromatic amino acid transporter TAT1 was shown previously to localize basolaterally in rat's small intestine and to mediate the efflux of L-Trp in the absence of exchange substrate, … Show more
“…Similarly, in rodents, oatp1c1 shows a strong expression in brain endothelial cells and in choroid plexus structures (6,12,45). MCT10, which is thought to act in the liver, intestine, kidneys, and growth plate chondrocytes in mammals (6,46,47), was observed in the liver and the trigeminal ganglia in zebrafish. Recently, OATP1C1 was implicated as compensating for the lack of MCT8 in MCT8-knock-out mice (12,48).…”
Background: Mutations in the thyroid hormone transporter MCT8 are associated with the psychomotor retardation Allan-Herndon-Dudley syndrome (AHDS). Results: In zebrafish, as in humans, mct8 is expressed primarily in the nervous system. Elimination of MCT8 causes severe neural impairment. Conclusion: MCT8 is a crucial regulator during zebrafish embryonic development. Significance: Establishment of the first vertebrate model for MCT8 deficiency, which exhibits a neurological phenotype.
“…Similarly, in rodents, oatp1c1 shows a strong expression in brain endothelial cells and in choroid plexus structures (6,12,45). MCT10, which is thought to act in the liver, intestine, kidneys, and growth plate chondrocytes in mammals (6,46,47), was observed in the liver and the trigeminal ganglia in zebrafish. Recently, OATP1C1 was implicated as compensating for the lack of MCT8 in MCT8-knock-out mice (12,48).…”
Background: Mutations in the thyroid hormone transporter MCT8 are associated with the psychomotor retardation Allan-Herndon-Dudley syndrome (AHDS). Results: In zebrafish, as in humans, mct8 is expressed primarily in the nervous system. Elimination of MCT8 causes severe neural impairment. Conclusion: MCT8 is a crucial regulator during zebrafish embryonic development. Significance: Establishment of the first vertebrate model for MCT8 deficiency, which exhibits a neurological phenotype.
“…Western blotting using oocyte protein lysates was performed as described previously (Ramadan et al 2006). …”
Section: Western Blot Analysismentioning
confidence: 99%
“…Quantitative Real Time PCR (qRT-PCR) was performed as described previously (Dave et al 2004;Ramadan et al 2006). Briefly, a 20 μl PCR reaction volume was prepared using cDNA (1 μl), TaqMan Universal PCR Master Mix (10 μl) (Applied Biosystems AG, Switzerland), Primers (0.8 μl each), Probe (0.4 μl) and DEPCWater (7 μl).…”
Section: Real Time Pcrmentioning
confidence: 99%
“…Whereas the gene expression along the human intestine has been described for some transporters (Kim et al 2002;Meier et al 2007;Terada et al 2005), to date information about the axial distribution of AA transporters along the digestive tract has been derived from animal studies (Dave et al 2004;Ramadan et al 2006;Takanaga et al 2005). Moreover, the data that is available from the human gut is difficult to interpret, since tissue specimens from different axial localizations originated from different patients and thus local expression differences might reflect discrepancies between patient groups (Terada et al 2005).…”
Section: Axial Distribution Of Intestinal Ace Ace2 Amino Acid and Pmentioning
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. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64
“…However, both MCT8 and MCT10 facilitate not only the cellular uptake but also the efflux of iodothyronines. Since MCT10 appears more important for the export than for the import of aromatic amino acids (Ramadan et al 2006(Ramadan et al , 2007, it is quite possible that cellular uptake of thyroid hormone is driven by the cellular efflux of aromatic amino acids through the same transporter. The trans-stimulation of T 3 and T 4 uptake by intracellular Trp has indeed been described in the studies of Francon and Blondeau (Zhou et al 1990(Zhou et al , 1992.…”
Thyroid hormone is a pleiotropic hormone with widespread biological actions. For instance, adequate levels of thyroid hormone are critical for the development of different tissues such as the central nervous system, but are also essential for the regulation of metabolic processes throughout life. The biological activity of thyroid hormone depends not only on serum thyroid hormone levels, but is also regulated at the tissue level by the expression and activity of deiodinases, which activate thyroid hormone or mediate its degradation. In addition, thyroid hormone transporters are necessary for the uptake of thyroid hormone into target tissues. With the discovery of monocarboxylate transporter 8 (MCT8) as a specific thyroid hormone transporter and the finding that mutations in this transporter lead to a syndrome of severe psychomotor retardation and elevated serum 3,3 0 ,5-tri-iodothyronine levels known as the Allan-Herndon-Dudley syndrome, the interest in this area of research has greatly increased. In this review, we will focus on the molecular aspects of thyroid hormone transporters, including MCT8, MCT10, organic anion transporting polypeptides, and the effects of genetic variation in these transporters.
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