Characterization of Microsomal GlutathioneS-Transferases MGST1, MGST2, and MGST3 in Cynomolgus Macaque

Abstract

The glutathione S-transferase (GST) family comprises cytosolic, mitochondrial, and microsomal GSTs, all essential enzymes that metabolize a wide range of endogenous and exogenous substrates. Among the microsomal GSTs (MGSTs) in humans, MGST1, MGST2, and MGST3 are involved in detoxification; however, MGSTs have not been fully investigated in cynomolgus macaque, an important primate species widely used in drug metabolism and toxicity studies. In the present study, cynomolgus MGST2 and MGST3 cDNAs were isolated from liver tissue and characterized along with previously isolated cynomolgus MGST1. For comparison with the cynomolgus cDNAs, MGST2 and MGST3 cDNAs were also isolated from rhesus macaque (closely related to cynomolgus macaque) liver. Cynomolgus MGST2 and MGST3, respectively, were highly identical (99 and 98%) to human MGST2 and MGST3 and nearly identical to the amino acid sequences of the rhesus orthologs, and they were closely clustered with human MGST2 and MGST3 by phylogenetic analysis. The analysis of genome data indicated that MGST1, MGST2, and MGST3, respectively, had similar gene structures and genomic organization in macaque and human. Therefore, cynomolgus MGSTs have molecular similarities to the corresponding human MGSTs. Cynomolgus MGST2 and MGST3 were expressed in liver, jejunum, and kidney, but at lower levels than MGST1. GST activities were measured with 1-chloro-2,4-dinitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)propane as substrates, using proteins heterologously expressed in Escherichia coli. Cynomolgus MGST1, MGST2, and MGST3 conjugated 1-chloro-2,4-dinitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)propane, indicating that cynomolgus MGST1, MGST2, and MGST3 are functional enzymes. These results suggest that these functional cynomolgus MGST enzymes and the corresponding human MGSTs are molecularly similar.

Soyabean glycinin depresses intestinal growth and function in juvenile Jian carp (Cyprinus carpiovar Jian): protective effects of glutamine

“…The GSTs represent an important group of enzymes that detoxify both endogenous compounds and foreign chemicals such as pharmaceuticals and environmental pollutants ( 56 ) . According to subcellular localisation, GSTs consists of cytosolic GST ( α , μ , π , ρ and θ ), mitochondrial GST κ and microsomal GST ( mGST1 , mGST2 and mGST3 ) ( 57 , 58 ) . Interestingly, this study observed that glycinin exposure caused decreases in the mRNA levels of all nine isoforms of GST, coinciding with GST enzyme activities.…”

Isolation and characterization of arylacetamide deacetylase in cynomolgus macaques

“…Cynomolgus macaques are frequently used in drug metabolism and toxicity studies due to their evolutionary closeness to humans. Our and other groups have identified and characterized a number of drug-metabolizing enzymes, including cytochromes P450, flavin-containing monooxygenases and glutathione S -transferases, and found generally similar molecular characteristics of these enzymes between cynomolgus macaques and humans [ 14 , 16 , 17 , 20 ]. Despite the importance of cynomolgus macaques in drug metabolism studies, AADAC has not been fully investigated partly due to the lack of molecular information on the cynomolgus AADAC.…”

Molecular assessment and transcriptome profiling of wild fish populations of Oryzias mekongensis and O. songkhramensis (Adrianichthyidae: Beloniformes) from Thailand

“…Hnrnpa1 is important regulation of RNA synthesis [57], but Histone-lysine N-methyltransferase EHMT1 exhibit functions in silencing of gene expression [58]. The Lpar6 is G protein-coupled receptor of lipid signaling [59], and the Mgst3 is essential gene in metabolize of endogenous and exogenous substrates [60]. In addition, Psmc5 plays the important processes for the maintenance of protein homeostasis [61].…”