Regulation of the Sodium/Sulfate Co-transporter by Farnesoid X Receptor α

Lee, Hans C.; Hubbert, Melissa L.; Osborne, Timothy F.; Woodford, Katherine; Zerangue, Noa; Edwards, Peter A.

doi:10.1074/jbc.m700897200

Cited by 6 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although these genes such as calcium transporter 1 and calbindin-D9K were not listed among the upregulated genes, it was reported that these gene expressions were induced during the transient suckling-weaning period in the mouse small intestine (42). Furthermore, we detected upregulation of Slc13a1, a transporter for sulfate that plays important roles in growth and development as a substrate for bone and cartilage (15,16), although it is unknown whether its expression is regulated by VDR. Further studies are required to investigate whether the induction of these gene expressions is regulated by VDR.…”

Section: Discussionmentioning

confidence: 75%

“…Interestingly, our microarray analyses revealed that the expressions of many genes belonging to the solute carrier family, which are related to absorption of nutrients/ions, were higher at the end of the weaning period (postnatal day 27) than at the start of the weaning period (day 13). Real-time RT-PCR analyses showed that Slc13a1, a transporter for sulfate, which has important roles in growth and development as a substrate for bone and cartilage (15,16), increased rapidly. Slc28a1, a transporter for nucleosides such as adenosine and uridine (17), and Slc16a3, a monocarboxylic acid transporter that transports lactic acid and pyruvate (18), were also upregulated at postnatal day 27.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

Mochizuki

Yorita

Goda

2009

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

SummaryIt is well-known that the small intestine of rodents rapidly undergoes differentiation and maturation during the transient suckling-weaning period from postnatal days 13 to 27. In the present study, we examined the gene expression changes in the jejunum of rats during the transient suckling-weaning period by microarray analysis. In the microarray data, we found that the expressions of many genes related to digestion/absorption/ excretion of nutrients/ions, such as members of the solute carrier ( Slc ) family and ATP-binding cassette ( Abc ) subfamily, were rapidly induced during this period. Furthermore, some transcriptional factors/cofactors ( Thrsp , Ppargc1a , Klf15 and Vdr ), which are presumably important for the induction of intestinal gene expression after weaning, were rapidly induced during this period. In contrast, genes related to transport of nutrients, such as folate, zinc, fat and phosphate, which are important for early development, were highly expressed in the suckling period and then gradually decreased during weaning. These results indicate that the jejunum matures during the suckling-weaning period accompanied by changes in the expression of many genes related to digestion/absorption/excretion and some genes for transcriptional factors/cofactors. Key Words transient suckling-weaning period, jejunum, solute carrier family, ATP-binding cassette subfamily, transcriptional factors/cofactorsThe morphology of the small intestine in rodents changes dramatically during the first 2-3 wk after birth as they are gradually weaned. During this period, the diet composition changes from one with less carbohydrate (milk) to one rich in carbohydrate (solid food) ( 1 ). Several studies have already shown that the expressions of genes related to carbohydrate digestion/absorption, such as disaccharidases [sucrase-isomaltase ( Si ) and trehalase ( Treh )], which are involved in the digestion of starch/sucrose or trehalose into monosaccharides, and hexose transporters [SGLT1 ( Slc5a1 ), GLUT5 ( Slc2a5 ) and GLUT2 ( Slc2a2 )], which are involved in monosaccharide absorption from the lumen, are elevated between 2 and 3 wk after birth in rodents ( 2 -5 ). In addition, we previously reported that the gene expressions of liver-type fatty acid-binding protein [L-FABP ( Fabp1 )] and cellular retinol-binding protein type II [CRBPII ( Rbp2 )], which are involved in transporting fatty acids and vitamin A, respectively, from the lumen to enterocytes, as well as a ␤ -oxidation rate-controlling gene [acyl-CoA oxidase ( Acox1 )], were highly expressed in the transient suckling-weaning period, and declined after weaning ( 6 , 7 ). Furthermore, the gene expression of peroxisome proliferator-activated receptor ␣ [PPAR ␣ ( Ppara )], a transcriptional factor for these genes, was associated with these gene expression changes ( 6 ).These changes during the transient suckling-weaning period may be regulated by the nutritional changes as well as hormones, such as thyroid hormone and glucocorticoid hormone, because such hormones ar...

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

Mochizuki

Yorita

Goda

2009

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

show abstract

“…Renal basal expression of Sult2a1 mRNA was also significantly lower in FXR knockout mice. These data suggest that when circulating bile acids are elevated, FXR activation in the renal tubular cells causes increased reabsorption of sulfate and sulfotransferase capacity to increase the excretion of sulfonated-bile acids in the urine (Lee et al, 2007). Thus, a similar mechanism may occur in the hepatocytes to normalize bile acid levels.…”

Section: Regulation Of Sult2a1 By Sulfate or Paps Deficiency 1509mentioning

confidence: 78%

“…Lee et al (2007) reported significantly higher renal NaS1 and Sult2a1 mRNA levels in mice after treatment with GW4064 or a-naphthylisothiocyanate, a hepatotoxin that is known to increase circulating bile acid levels, and identified NaS1 as a novel target gene of FXR. When FXR was knocked out, basal expression of renal and intestinal NaS1 was significantly reduced, and a-naphthylisothiocyanate treatment did not increase NaS1 expression.…”

Section: Regulation Of Sult2a1 By Sulfate or Paps Deficiency 1509mentioning

confidence: 99%

Regulation of Murine Hepatic Hydroxysteroid Sulfotransferase Expression in Hyposulfatemic Mice and in a Cell Model of 3′-Phosphoadenosine-5′-Phosphosulfate Deficiency

et al. 2013

View full text Add to dashboard Cite

The cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of nucleophilic substrates, and the cofactor for sulfonation, 39-phosphoadenosine-59-phosphosulfate (PAPS), is biosynthesized from sulfate and ATP. The phenotype of male knockout mice for the NaS1 sodium sulfate cotransporter includes hyposulfatemia and increased hepatic expression of mouse cytoplasmic sulfotransferase Sult2a and Sult3a1. Here we report that in 8-week-old female NaS1-null mice, hepatic Sult2a1 mRNA levels were ∼51-fold higher than they were in a wild-type liver but expression of no other Sult was affected. To address whether hyposulfatemia-inducible Sult2a1 expression might be due to reduced PAPS levels, we stably knocked down PAPS synthases 1 and 2 in HepG2 cells (shPAPSS1/2 cells). When a reporter plasmid containing at least 233 nucleotides (nt) of Sult2a1 59-flanking sequence was transfected into shPAPSS1/2 cells, reporter activity was significantly increased relative to the activity that was seen for reporters containing 179 or fewer nucleotides.Mutation of an IR0 (inverted repeat of AGGTCA, with 0 intervening bases) nuclear receptor motif at nt 2191 to 180 significantly attenuated the PAPSS1/2 knockdown-mediated increase. PAPSS1/2 knockdown significantly activated farnesoid X receptor (FXR), retinoid-related orphan receptor, and pregnane X receptor responsive reporters, and treatment with the FXR agonist GW4064 [3-(2,6-dichlorophenyl)-4-(39-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole] increased Sult2a1 promoter activity when the IR0 was intact. Transfection of shPAPSS1/2 cells with FXR small interfering RNA (siRNA) significantly reduced the Sult2a1 promoter activity. The impact of PAPSS1/2 knockdown on Sult2a1 promoter activity was recapitulated by knocking down endogenous SULT2A1 expression in HepG2 cells. We propose that hyposulfatemia leads to hepatic PAPS depletion, which causes loss of SULT2A1 activity and results in accumulation of nonsulfated bile acids and FXR activation.

show abstract

“…More important is endogenous oxalate, which is a metabolic end product, mainly derived from ascorbic acid and glycine [6]. Interestingly, serum sulfate levels were not statistically different between wild type and knock out animals [13], while mice lacking the vitamin D receptor have both, hypersulfaturia and hyposulfatemia [2].In this issue of the Journal of Hepatology, a study identifies glyoxylate as a substrate of Sat-1 and demonstrates a role of glyoxylate in the regulation of Sat-1 expression [21]. The role of the gut in oxalate homeostasis gains importance with progression of renal failure [3] and is highlighted by the observation that patients with a short bowel have a considerable risk of developing calcium oxalate renal stones [18].…”

mentioning

confidence: 96%

Regulation of the expression of the hepatocellular sulfate–oxalate exchanger SAT-1 (SLC26A1) by glyoxylate: A metabolic link between liver and kidney?

Stieger¹

2011

Journal of Hepatology

View full text Add to dashboard Cite

See Article, pages 513-520The liver and kidney are the key organs in detoxification of endogenous and exogenous substances from the body. Detoxification of lipophilic endogenous substances and lipophilic xenobiotics involves biotransformation. This process starts with functionalization of the molecule, often by a member of the family of cytochrome P450 enzymes, followed by conjugation with a hydrophilic molecule, e.g. by glucuronidation or sulfonation. In the case of sulfonation, the sulfate donor for sulfotransferases is 3 0 -phosphoadenosine 5 0 -phosphosulfate, which is synthesized from sulfate and ATP [9]. Hence, ongoing sulfonation requires supply of sulfate as inorganic anion. Furthermore, sulfation is an important post-translational modification of proteins. In the body, sulfate transport is mediated by two different types of transporters: secondary active sodium-dependent transporters and sodium-independent sulfate/anion exchangers [17]. The role of sulfate transporters in detoxification is highlighted by the observation that mice with a disrupted gene for the sodiumdependent sulfate transporter NaS1 (Slc13a1) or the sodiumindependent sulfate anion transporter Sat-1 (Slc26a1) display hypersulfaturia, hyposulfatemia and increased sensitivity to acetaminophen induced liver injury [5,14], while the role of sulfate transporters in post-translational protein modification is evidenced by lethal and nonlethal disorders in patients with mutations in sulfate transporters [10,12,20] and an impaired intestinal barrier function in mice with a disrupted gene for NaS1 [4].Sat1 is the founding member of the SLC26A family, was cloned from rat liver [1] and is localized to the basolateral plasma membrane of hepatocytes and kidney proximal tubular cells, respectively [8,19]. It acts as an anion exchanger and transports, in addition to sulfate, also chloride, bicarbonate, and oxalate in an electroneutral manner [1,11]. The oxalate pool is fed by dietary oxalate and as such absorbed to a minor extent in the intestine [6]. More important is endogenous oxalate, which is a metabolic end product, mainly derived from ascorbic acid and glycine [6]. Elimination of oxalate from the body is complex, but seems to occur predominantly via the kidney [15] and to a minor extent by the gut. The role of the gut in oxalate homeostasis gains importance with progression of renal failure [3] and is highlighted by the observation that patients with a short bowel have a considerable risk of developing calcium oxalate renal stones [18]. Urolithiasis is also observed in mice with a disrupted Sat1 gene [5]. Therefore, Sat1 may not only be an important transporter involved in sulfate homeostasis but also plays a critical role in the proper excretion of oxalate from the body. Sat-1, therefore, seems to play a broad role in detoxification. Sulfate homeostasis is predominantly, if not exclusively, regulated via renal elimination [16], which also applies to oxalate [15].It is evident from these physiologic and pathophysiologic aspects that understanding ...

show abstract

Regulation of the Sodium/Sulfate Co-transporter by Farnesoid X Receptor α

Cited by 6 publications

References 41 publications

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

Regulation of Murine Hepatic Hydroxysteroid Sulfotransferase Expression in Hyposulfatemic Mice and in a Cell Model of 3′-Phosphoadenosine-5′-Phosphosulfate Deficiency

Regulation of the expression of the hepatocellular sulfate–oxalate exchanger SAT-1 (SLC26A1) by glyoxylate: A metabolic link between liver and kidney?

Contact Info

Product

Resources

About