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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 6 different splice variants of TXNRD1. In fetal liver samples (N = 59) α7/8 was the most abundant transcript, and significantly higher than the other variants (p < 0.001). In the adult liver samples (N = 17) α13 was found at high levels in some but not in all samples, i.e. there was a large inter-subject variation. The average expressions of α7/8 and α1/2 were significantly higher compared to α6 and α10/11. Statistical analysis were performed using Kruskal–Wallis test followed by Dunn’s multiple comparison post-test for identification of which groups differed from the other.
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f0010: Relative mRNA expression of 6 different splice variants of TXNRD1. In fetal liver samples (N = 59) α7/8 was the most abundant transcript, and significantly higher than the other variants (p < 0.001). In the adult liver samples (N = 17) α13 was found at high levels in some but not in all samples, i.e. there was a large inter-subject variation. The average expressions of α7/8 and α1/2 were significantly higher compared to α6 and α10/11. Statistical analysis were performed using Kruskal–Wallis test followed by Dunn’s multiple comparison post-test for identification of which groups differed from the other.

Mentions: In fetal liver samples α7/8 was the most abundant transcript, three times higher than the wildtype α1/2 (p < 0.001), whereas the isoforms α13 and γ2–4 were found at lowest levels (Fig. 2). In the adult liver samples α13 was found at the highest levels, but with a large inter-subject variation (200-fold). Isoform α6 was present at the lowest levels compared to the other isoforms (Fig. 2).


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 6 different splice variants of TXNRD1. In fetal liver samples (N = 59) α7/8 was the most abundant transcript, and significantly higher than the other variants (p < 0.001). In the adult liver samples (N = 17) α13 was found at high levels in some but not in all samples, i.e. there was a large inter-subject variation. The average expressions of α7/8 and α1/2 were significantly higher compared to α6 and α10/11. Statistical analysis were performed using Kruskal–Wallis test followed by Dunn’s multiple comparison post-test for identification of which groups differed from the other.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0010: Relative mRNA expression of 6 different splice variants of TXNRD1. In fetal liver samples (N = 59) α7/8 was the most abundant transcript, and significantly higher than the other variants (p < 0.001). In the adult liver samples (N = 17) α13 was found at high levels in some but not in all samples, i.e. there was a large inter-subject variation. The average expressions of α7/8 and α1/2 were significantly higher compared to α6 and α10/11. Statistical analysis were performed using Kruskal–Wallis test followed by Dunn’s multiple comparison post-test for identification of which groups differed from the other.
Mentions: In fetal liver samples α7/8 was the most abundant transcript, three times higher than the wildtype α1/2 (p < 0.001), whereas the isoforms α13 and γ2–4 were found at lowest levels (Fig. 2). In the adult liver samples α13 was found at the highest levels, but with a large inter-subject variation (200-fold). Isoform α6 was present at the lowest levels compared to the other isoforms (Fig. 2).

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.