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Prenatal expression of thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1) in humans.

Björkhem-Bergman L, Johansson M, Morgenstern R, Rane A, Ekström L - FEBS Open Bio (2014)

Bottom Line: Of the six studied splice variants of TXNRD1, four had a significantly higher expression in the fetal livers as compared to adult livers.Treatment with the demethylating agent 5-AZA resulted in decreased levels of TXNRD1 in human liver HepG2 cells but did not affect the expression of MGST1.In conclusion, the expression of TXNRD1 is higher in fetuses than in adults and might be of importance during fetal life.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.

ABSTRACT
Thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1) are important redox and detoxifying enzymes in adult life. The aim of this study was to investigate the expression of these enzymes during fetal life. In addition, the role of gene methylation was studied since this might play an important role in the on-and-off switch of gene expression between fetal and adult life. To this end, the expression of the TRXR1-encoding gene TXNRD1 and the MGST1-encoding gene MGST1 was studied in fetal tissues. The mean mRNA expression of TXNRD1 in fetal livers were seven times higher compared to the mean expression in adult livers (p < 0.001). Of the six studied splice variants of TXNRD1, four had a significantly higher expression in the fetal livers as compared to adult livers. The mean expression of MGST1 was twofold higher in adult compared to fetal liver tissue (p = 0.01). For MGST1 the alternative first exon 1B was the predominant splice variant in both fetal and adult liver samples. The highest mRNA expression of both TXNRD1 and MGST1 was found in fetal adrenals, whereas expression was lower in fetal liver, lungs and kidneys. There was a significant correlation between the hepatic expression of TXNRD1 and MGST1. Treatment with the demethylating agent 5-AZA resulted in decreased levels of TXNRD1 in human liver HepG2 cells but did not affect the expression of MGST1. In conclusion, the expression of TXNRD1 is higher in fetuses than in adults and might be of importance during fetal life. Hepatic TXNRD1 and MGST1 are co-expressed in both fetuses and adults suggesting common regulatory mechanisms.

No MeSH data available.


Relative mRNA expression of TXNRD1 and MGST1 mRNA in 59 fetal and 17 adult liver tissue samples. There was a 7-fold higher expression of TXNRD1 in fetal than adult liver tissue (p < 0.001). In contrast, there was a 2-fold higher expression of MGST1 in adult compared to fetal liver tissue (p = 0.01). Statistical analyses were performed using Mann–Whitney test.
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f0005: Relative mRNA expression of TXNRD1 and MGST1 mRNA in 59 fetal and 17 adult liver tissue samples. There was a 7-fold higher expression of TXNRD1 in fetal than adult liver tissue (p < 0.001). In contrast, there was a 2-fold higher expression of MGST1 in adult compared to fetal liver tissue (p = 0.01). Statistical analyses were performed using Mann–Whitney test.

Mentions: In order to compare the TXNRD1 mRNA expression between adult and fetal liver samples we used primers that bind to exon 5 and exon 6. TXNRD1 was detectable in 59 of 60 fetal and 17 of 20 adult liver samples. Significantly higher levels of TXNRD1 mRNA transcripts were observed in the fetal liver samples as compared to the adult liver samples. The mean TXNRD1 was 7 times higher in fetal liver compared to adult liver (mean 12.8 ± 0.82 vs mean 1.82 ± 0.48; p < 0.0001) as shown in Fig. 1. In the adults specimens a larger inter-individual variation in TXNRD1 mRNA was found (90-fold) compared to the fetal specimens in which a 30-fold variation was found.


Prenatal expression of thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1) in humans.

Björkhem-Bergman L, Johansson M, Morgenstern R, Rane A, Ekström L - FEBS Open Bio (2014)

Relative mRNA expression of TXNRD1 and MGST1 mRNA in 59 fetal and 17 adult liver tissue samples. There was a 7-fold higher expression of TXNRD1 in fetal than adult liver tissue (p < 0.001). In contrast, there was a 2-fold higher expression of MGST1 in adult compared to fetal liver tissue (p = 0.01). Statistical analyses were performed using Mann–Whitney test.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215115&req=5

f0005: Relative mRNA expression of TXNRD1 and MGST1 mRNA in 59 fetal and 17 adult liver tissue samples. There was a 7-fold higher expression of TXNRD1 in fetal than adult liver tissue (p < 0.001). In contrast, there was a 2-fold higher expression of MGST1 in adult compared to fetal liver tissue (p = 0.01). Statistical analyses were performed using Mann–Whitney test.
Mentions: In order to compare the TXNRD1 mRNA expression between adult and fetal liver samples we used primers that bind to exon 5 and exon 6. TXNRD1 was detectable in 59 of 60 fetal and 17 of 20 adult liver samples. Significantly higher levels of TXNRD1 mRNA transcripts were observed in the fetal liver samples as compared to the adult liver samples. The mean TXNRD1 was 7 times higher in fetal liver compared to adult liver (mean 12.8 ± 0.82 vs mean 1.82 ± 0.48; p < 0.0001) as shown in Fig. 1. In the adults specimens a larger inter-individual variation in TXNRD1 mRNA was found (90-fold) compared to the fetal specimens in which a 30-fold variation was found.

Bottom Line: Of the six studied splice variants of TXNRD1, four had a significantly higher expression in the fetal livers as compared to adult livers.Treatment with the demethylating agent 5-AZA resulted in decreased levels of TXNRD1 in human liver HepG2 cells but did not affect the expression of MGST1.In conclusion, the expression of TXNRD1 is higher in fetuses than in adults and might be of importance during fetal life.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.

ABSTRACT
Thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1) are important redox and detoxifying enzymes in adult life. The aim of this study was to investigate the expression of these enzymes during fetal life. In addition, the role of gene methylation was studied since this might play an important role in the on-and-off switch of gene expression between fetal and adult life. To this end, the expression of the TRXR1-encoding gene TXNRD1 and the MGST1-encoding gene MGST1 was studied in fetal tissues. The mean mRNA expression of TXNRD1 in fetal livers were seven times higher compared to the mean expression in adult livers (p < 0.001). Of the six studied splice variants of TXNRD1, four had a significantly higher expression in the fetal livers as compared to adult livers. The mean expression of MGST1 was twofold higher in adult compared to fetal liver tissue (p = 0.01). For MGST1 the alternative first exon 1B was the predominant splice variant in both fetal and adult liver samples. The highest mRNA expression of both TXNRD1 and MGST1 was found in fetal adrenals, whereas expression was lower in fetal liver, lungs and kidneys. There was a significant correlation between the hepatic expression of TXNRD1 and MGST1. Treatment with the demethylating agent 5-AZA resulted in decreased levels of TXNRD1 in human liver HepG2 cells but did not affect the expression of MGST1. In conclusion, the expression of TXNRD1 is higher in fetuses than in adults and might be of importance during fetal life. Hepatic TXNRD1 and MGST1 are co-expressed in both fetuses and adults suggesting common regulatory mechanisms.

No MeSH data available.