Prenatal expression of thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1) in humans.
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.
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Linda
L
Björkhem-Bergman
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Maria
M
Johansson
Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Ralf
R
Morgenstern
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Anders
A
Rane
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
Lena
L
Ekström
5-AZA, 5-AZA-2-deoxyxytidine; DNA methylation; Fetus; Liver; MGST1, microsomal glutathione transferase 1; Microsomal glutathione transferase 1; Splice variants; TRXR1, thioredoxin reductase 1; Thioredoxin reductase 1