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

Björkhem‐Bergman, Linda; Johansson, Maria H.; Morgenstern, Ralf; Rane, Anders; Ekström, Lena

doi:10.1016/j.fob.2014.10.005

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…It has been reported that active function of AKR1C1 as a key component of the STAT3 pathway may promote lung cancer metastasis 59,60 . MGST2, the member of MGST family, primarily metabolizes foreign chemicals, such as drugs and environmental pollutants, and also plays roles in the detoxification of reactive compounds 61 . These data suggest that UGT2B/AKR1C1/MGST2 variants are potential predictive biomarkers for cetuximab resistance.…”

Section: Discussionmentioning

confidence: 92%

New genetic variations discovered in KRAS wild‐type cetuximab resistant chinese colorectal cancer patients

Jing

Wang

et al. 2020

Molecular Carcinogenesis

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To perform a comprehensive genomic analysis of colorectal cancer (CRC) tumor to detect genetic variants and identify novel resistant mutations associated with cetuximab‐resistance in CRC patients. A retrospective study was performed using whole exome sequencing (WES) to identify common genetic factors from 22 cetuximab‐sensitive and 10 cetuximab‐resistant patients. In all 10 cetuximab‐resistant patients, we discovered there are 37 significantly mutated genes (SMGs). CYP4A11 was the most frequently mutated gene in cetuximab‐resistant patients. BCAS1 and GOLGA6L1 were found to be among the second group of frequently mutated genes with a frequency of 60%. After cosine similarity analysis, three mutational signatures (signature a, b, and c) were found in all CRC tumors, similar to signature 1, 5, and 6 in COSMIC, respectively. Gene ontology analysis was performed on SMGs and found 12 enriched GO terms. Four genes are enriched in six specific Kyoto Encyclopedia of Genes and Genomes pathway groups, including the metabolism of xenobiotics by cytochrome P450, steroid hormone biosynthesis, retinol metabolism, and drug metabolism. Our data supports a network composed of SMGs and cellular signaling pathways that have been positively linked to the mechanisms of cetuximab resistance. These involve DNA damage repair, angiogenesis, invasion, drug metabolism, and the CRC tumor microenvironment. There is a SMG, OR9G1 correlated with survival rates of KRAS wild‐type colon adenocarcinoma patients. These findings support further investigation using WES in a prospective clinical study of cetuximab resistance CRC, to further identify, confirm, and extend the clinical significance of these and other potentially important new candidate predictive biomarkers of cetuximab response.

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Section: Discussionmentioning

confidence: 92%

New genetic variations discovered in KRAS wild‐type cetuximab resistant chinese colorectal cancer patients

Jing

Wang

et al. 2020

Molecular Carcinogenesis

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“…Another factor shown to be protective is microsomal glutathione transferase-1 (MGST1), which accumulates in mitochondria and is protective from oxidative stress (Siritantikorn et al, 2007). It has been observed that MGST1 expression was very low in neuroblastomas and neuroblastoma cell line (Bjorkhem-Bergman et al, 2014). These authors hypothesized that this could explain the extreme sensitivity of neuroblastomas to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Differences in Gene Expression Profiles and Phenotypes of Differentiated SH-SY5Y Neurons Stably Overexpressing Mitochondrial Ferritin

Mendsaikhan

Takeuchi

Walker

et al. 2019

Front. Mol. Neurosci.

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Mitochondrial ferritin (FtMt) is an iron-transport protein with ferroxidase properties localized to mitochondria. Levels are generally low in all tissues, while increasing the expression of FtMt in neuronal-like cells has been shown to be protective. To determine whether FtMt has potential as a therapeutic approach, there remains the question of how much FtMt is protective. To address this issue, we transfected SH-SY5Y neuroblastoma cells with a FtMt expression plasmid and isolated cell lines with stable expression of FtMt at high, medium and low levels. Using these cell lines, we examined effects of FtMt on neuronal phenotype, neuroprotective activity and gene expression profiles. The phenotypic properties of high, medium and low FtMt expressors were compared with native untransfected SH-SY5Y cells after differentiation with retinoic acid to a neuronal phenotype. Overexpression of FtMt, even in low expressing cells, showed significant protection from oxidative stress induced by hydrogen peroxide or cobalt chloride. Higher levels of FtMt expression did not appear to offer greater protection, and did not have toxic consequences to cells, even though there were significantly more aggregated mitochondria in the highest expressing clone. The phenotypes differed between cell clones when assessed by cell growth, neurite outgrowth, and expression of neuronal proteins including those associated with neurodegenerative diseases. Microarray analysis of high, medium and negative FtMt-expressing cells identified different patterns of expression of certain genes associated with oxidative stress and neuronal development, amongst others. Validation of microarray analyses was carried out by real time polymerase chain reaction. The results showed significant differences in expression of thioredoxin-interacting protein (TXNIP) and microsomal glutathione transfer-1 (MGST-1), which can have critical roles in the regulation of oxidative stress. Differences in expression of calcitonin-related polypeptide alpha (CALCA), growth differentiation factor-15 (GDF-15) and secretogranin II (SCG2) were also observed. Our findings indicate that even low levels of increased FtMt expression can be protective possibly by alterations of some oxidative stress-related and growth factor genes, while high levels of expression did not appear to offer greater protection from oxidative stress or induce significant toxicity in cells. These experiments provide supporting data that increasing FtMt might be a feasible strategy for therapeutics in certain neurodegenerative and neurological diseases.

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“…Third, Sll1147 and other prokaryotic and eukaryotic MAPEG enzymes produced from recombinant E. coli strains were only shown to have the classical in vitro GST activity, which is the conjugation of GSH with the standard 1-chloro-2,4-dinitrobenzene (CDNB) exogenous agent (Bresell et al, 2005). Fourth, the analysis of the selectivity/redundancy of GSTs is bound to be easier in a well-studied basic organism such as Synechocystis than in higher eukaryotes that possess (i) various tissues (Morgenstern et al, 2011), (ii) complex developmental processes (Björkhem-Bergman et al, 2014) and (iii) large enzyme families. For example, 27 GST encoding genes were identified in human and classified into 7 classes (Alpha, Mu, Pi, Theta, Omega, Zeta, Kappa, and MAPEG) (Nebert and Vasiliou, 2004) whereas Synechocystis possesses only six GSTs including Sll1147.…”

Section: Discussionmentioning

confidence: 99%

From Cyanobacteria to Human, MAPEG-Type Glutathione-S-Transferases Operate in Cell Tolerance to Heat, Cold, and Lipid Peroxidation

2019

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The MAPEG2 sub-family of glutathione-S-transferase proteins (GST) has been poorly investigated in vivo, even in prokaryotes such as cyanobacteria the organisms that are regarded as having developed glutathione-dependent enzymes to protect themselves against the reactive oxygen species (ROS) often produced by their powerful photosynthesis. We report the first in vivo analysis of a cyanobacterial MAPEG2-like protein (Sll1147) in the model cyanobacterium Synechocystis PCC 6803. While Sll1147 is dispensable to cell growth in standard photo-autotrophic conditions, it plays an important role in the resistance to heat and cold, and to n-tertbutyl hydroperoxide (n-tBOOH) that induces lipid peroxidation. These findings suggest that Sll1147 could be involved in membrane fluidity, which is critical for photosynthesis. Attesting its sensitivity to these stresses, the Δsll1147 mutant lacking Sll1147 challenged by heat, cold, or n-tBOOH undergoes transient accumulation of peroxidized lipids and then of reduced and oxidized glutathione. These results are welcome because little is known concerning the signaling and/or protection mechanisms used by cyanobacteria to cope with heat and cold, two inevitable environmental stresses that limit their growth, and thus their production of biomass for our food chain and of biotechnologically interesting chemicals. Also interestingly, the decreased resistance to heat, cold and n-tBOOH of the Δsll1147 mutant could be rescued back to normal (wild-type) levels upon the expression of synthetic MAPEG2-encoding human genes adapted to the cyanobacterial codon usage. These synthetic hmGST2 and hmGST3 genes were also able to increase the Escherichia coli tolerance to heat and n-tBOOH. Collectively, these finding indicate that the activity of the MAPEG2 proteins have been conserved, at least in part, during evolution from (cyano)bacteria to human.

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

Cited by 11 publications

References 27 publications

New genetic variations discovered in KRAS wild‐type cetuximab resistant chinese colorectal cancer patients

New genetic variations discovered in KRAS wild‐type cetuximab resistant chinese colorectal cancer patients

Differences in Gene Expression Profiles and Phenotypes of Differentiated SH-SY5Y Neurons Stably Overexpressing Mitochondrial Ferritin

From Cyanobacteria to Human, MAPEG-Type Glutathione-S-Transferases Operate in Cell Tolerance to Heat, Cold, and Lipid Peroxidation

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