Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal models have been extensively used in the study of cardiovascular disease (CVD) and have provided important insights into disease pathogenesis and drug development. However, the level of conservation of gene expression patterns of the orthologous genes between human and animal models was unclear. To address this issue, we compared the expression of orthologous genes in human and four models (rhesus, rat, mouse and dog), based on 42 normal heart samples with high quality gene expression data. The results show that the global expression profiles between animal model and human orthologous genes are highly preserved. The phylogenetic tree inferred from the gene expression profiles has similar topology to that of the species tree. However, differentially expressed genes (DEGs) between human and each model were identified and these four gene datasets are enriched with different molecular functions, including hormone-receptor binding and geranyl transferase activity. The 65 overlapped DEGs between four sets are involved in thyroid cancer, proteasome systems, aminoacyl-tRNA biosynthesis and GST (Glycine, Serine and Threonine) metabolism, of which functions are divergent between models and humans. In addition, 46.2% (30/65) of the communal genes have been experimentally proven to be associated with cardiovascular disease. Next, we constructed a co-expression network based on intra- and inter-species variation, to elucidate the altered network organization. It indicates that these DEGs evolved as modules rather than independently. The integrated heart transcriptome data should provide a valuable resource for the in-depth understanding of cardiology and the development of cardiovascular disease models.
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PMID:A systematic analysis of heart transcriptome highlights divergent cardiovascular disease pathways between animal models and humans. 2215 53

Bcl-2 associated athanogene 3 (BAG3) has a modular structure that contains a BAG domain, a WW domain, a proline-rich (PxxP) domain to mediate potential interactions with chaperons and other proteins that participate in more than one signal transduction. In search for novel interacting partners, the current study identified that 78kDa glucose-regulated protein (GRP78) was a novel partner interacting with BAG3. Interaction between GRP78 and BAG3 was confirmed by coimmunoprecipitation and glutathione S-transferase (GST) pulldown. We also identified that the ATPase domain of GRP78 and BAG domain of BAG3 mediated their interaction. Counterintuitive for a prosurvival protein, BAG3 was found to promote the cytotoxicity of breast cancer MCF7, thyroid cancer FRO and glioma U87 cells subjected to genotoxic stress. In addition, the current study demonstrated that BAG3 interfered with the formation of the antiapoptotic GRP78-procaspase-7 complex, which resulted in an increased genotoxic stress-induced cytotoxicity in cancer cells. Furthermore, overexpression of GRP78 significantly blocked the enhancing effects of BAG3 on activation of caspase-7 and induction of apoptosis by genotoxic stress. Overall, these results suggested that through direct interaction BAG3 could prevent the antiapoptotic effect of GRP78 upon genotoxic stress.
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PMID:BAG3 sensitizes cancer cells exposed to DNA damaging agents via direct interaction with GRP78. 2408 88

Korea has the highest incidence of thyroid cancer of any nation. We conducted a population-based, case-control study of the association between the risk of papillary thyroid cancer (PTC) in the Korean population and polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T, glutathione S-transferase class mu (GSTM1), and glutathione S-transferase class theta (GSTT1). The study subjects consisted of 2,194 newly diagnosed PTC cases and 1,669 population-based healthy controls. Odds ratios adjusted by age, sex, body mass index, smoking, drinking, serum thyroid-stimulating hormone level, family history of thyroid cancer, and previous history of thyroid disease, with 95% confidence intervals, were estimated using logistic regression analysis. The frequencies of MTHFR 677TT genotypes, and null genotypes of GSTM1 and GSTT1 were 19.2, 56.8, and 51.4% among PTC cases and 17.4, 54.1, and 50.6% among the controls, respectively. No significant associations between PTC and TT genotypes of MTHFR C677T, null genotypes of GSTM1 and GSTT1, or double-null (GSTM1-GSTT1) genotypes were found. These findings suggest that polymorphisms of the MTHFR C677T, GSTM1 and GSTT1 genotypes do not contribute to the development of PTC susceptibility in the Korean population.
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PMID:Polymorphisms of methylenetetrahydrofolate reductase and glutathione S-transferase are not associated with the risk of papillary thyroid cancer in Korean population. 2453 71


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