Expression of the sulfotransferase 1C family: implications for xenobiotic toxicity

Runge‐Morris, Melissa; Kocarek, Thomas A.

doi:10.3109/03602532.2013.835634

Cited by 31 publications

(20 citation statements)

References 48 publications

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“…These enzymes play an important role in the metabolism of drugs (20) and toxins as well as in detoxification (21,22). Using 2-AF as an example, the process by which arylamines cause cancer is as follows: first, NATs in the cell transform 2-AF into N-acetyl-2-aminofluorene (2-AAF) (23), then 2-AAF is further activated by other enzymes such as glucuronyltransferase, deacylase, sulfotransferase and acyltransferase (24,25), and ultimately transformed in the end to carcinogens nitrenium ion and arylamidonium ion. These can react with guanines to produce bulky adducts of N-deoxyguanaminofluorene and N-deoxyguanacetaminofluorene, which are DNA-carcinogenic compounds.…”

Section: Discussionmentioning

confidence: 99%

The effect of α-solanine on the activity, gene expression, and kinetics of arylamine N-acetyltransferase in HepG2 cells

et al. 2018

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α-solanine is one of the major components of Solanum nigrum Linn., the fruits of which are used in China for food. In the present study, α-solanine was selected to assess the inhibition of arylamine N-acetyltransferase (NAT) activity and mRNA expression of NAT and kinetics in HepG2 cells. NAT activity was examined by HPLC. The double-reciprocal plot was contrived to yield a regression equation to calculate Km and Vmax. NAT mRNA expression was determined by PCR. The results revealed that α-solanine could significantly decrease NAT activity in intact HepG2 cells or the cytoplasm. Km did not differ either for intact HepG2 cells or for the cytoplasm, however Vmax was significantly different. α-solanine could decrease the expression of NAT1 mRNA and NAT2 mRNA. In summary, α-solanine was a non-competitive inhibitor of NAT in HepG2 cells. It decreased NAT activity through non-competitive inhibition of NAT activity and by decreasing the expression of NAT1 mRNA and NAT2 mRNA.

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Section: Discussionmentioning

confidence: 99%

The effect of α-solanine on the activity, gene expression, and kinetics of arylamine N-acetyltransferase in HepG2 cells

et al. 2018

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“…Previous studies have shown that the SULT1Cs are predominantly expressed in the human fetus; therefore, researchers in the field hypothesize that the primary role of these enzymes is to metabolize endogenous and exogenous signaling molecules involved in growth and differentiation during human fetal development [12–14, 41]. Sulfonation and desulfonation pathways are involved in the regulation of hormones (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies on the hSULT1C subfamily have shown that these isoforms convert various xenobiotics, such as procarcinogens, into reactive metabolites; however, their function in endogenous metabolism and physiology has not yet been well characterized [9–11]. Although the hSULT1C subfamily’s substrate specificity remains unclear, hSULT1C4 (previously referred to as SULT1C2) is highly expressed in the fetal lung and fetal kidney, with lower expression in fetal heart, adult kidney, ovary, brain and spinal cord [12–14]. Due to hSULT1C4’s fetal expression, one of the physiological functions of this enzyme may be to metabolize and regulate endogenous and exogenous signaling molecules during fetal development.…”

Section: Introductionmentioning

confidence: 99%

Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4

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Runge‐Morris

et al. 2017

Hormone Molecular Biology and Clinical Investigation

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Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3′-phosphoadenosine-5′-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the mother during fetal development. Human SULT1C4 has previously been shown to sulfonate estrogenic compounds, such as catechol estrogens; therefore, this study focused on the expression and purification of hSULT1C4 in order to further characterize this enzyme’s sulfonation of estrogenic compounds. Molecular modeling of the enzyme’s native properties helped to establish a novel purification protocol for hSULT1C4. The optimal activity assay conditions for hSULT1C4 were determined to be pH 7.4 at 37°C for up to 10 min. Kinetic analysis revealed the enzyme’s reduced affinity for PAPS compared to PAP. Human SULT1C4 sulfonated all the estrogenic compounds tested, including dietary flavonoids and environmental estrogens; however, the enzyme has a higher affinity for sulfonation of flavonoids. These results suggest hSULT1C4 could be metabolizing and regulating hormone signaling pathways during human fetal development.

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“…These three genes and one pseudogene, SULT1C2P1, are located in a cluster on chromosome 2 Runge-Morris and Kocarek, 2013). Of these genes, SULT1C2 (sometimes called SULT1C1 in the literature) and SULT1C4 (sometimes called SULT1C2 in the literature) have been cloned, expressed, and partially characterized (Her et al, 1997;Sakakibara et al, 1998;Stanley et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Expression of the Orphan Cytosolic Sulfotransferase SULT1C3 in Human Intestine: Characterization of the Transcript Variant and Implications for Function

et al. 2013

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The cystolic sulfotransferse 1C3 (SULT1C3) gene was identified by computational analysis of the human genome and suggested to contain duplications of its last two exons (7a/b and 8a/b). Although the SULT1C3 isoform containing the more downstream exons 7b and 8b (SULT1C3d) has been expressed in Escherichia coli, crystallized, and characterized for activity, there is currently no evidence that SULT1C3 is expressed in any human tissue. Using reversetranscription polymerase chain reaction, we detected SULT1C3 mRNA in the colorectal adenocarcinoma cell line (LS180), colon, and small intestine, but the amplified fragment contained the more upstream exons 7a and 8a. 39-Rapid amplification of cDNA ends (RACE) confirmed that the SULT1C3 transcript expressed in LS180 cells contained exons 7a/8a, whereas 59-RACE identified a noncoding exon 1. Full-length SULT1C3 transcript containing exons 7a/8a was amplified from LS180 and intestinal RNA, and in vitro transcription-translation of the cloned cDNA indicated that translation primarily began at the first of three in-frame ATG codons. Since SULT1C3 containing exons 7a/8a (SULT1C3a) would differ by 30 amino acids from SULT1C3d containing exons 7b/8b, we considered the functional implications of expressing one or the other isoform by generating structural models based on the reported crystal structure for SULT1C3d. Comparison of the structures indicated that five of the residues forming the substrate-binding pocket differed between the two isoforms, resulting in a change in both electron density and charge distribution along the inner wall of the substrate-binding pocket. These data indicate that SULT1C3 is expressed in human intestine but suggest that the expressed isoform is likely to differ functionally from the isoform that has been previously characterized.

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Expression of the sulfotransferase 1C family: implications for xenobiotic toxicity

Cited by 31 publications

References 48 publications

The effect of α-solanine on the activity, gene expression, and kinetics of arylamine N-acetyltransferase in HepG2 cells

The effect of α-solanine on the activity, gene expression, and kinetics of arylamine N-acetyltransferase in HepG2 cells

Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4

Expression of the Orphan Cytosolic Sulfotransferase SULT1C3 in Human Intestine: Characterization of the Transcript Variant and Implications for Function

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