Project description:Glutathione S-transferase omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. In this study we show that silencing of GSTO1 with siRNA significantly impairs cancer cell viability, validating GSTO1 as a potential new target in oncology. We report on the development and characterization of a series of chloroacetamide-containing potent GSTO1 inhibitors. Co-crystal structures of GSTO1 with our inhibitors demonstrate covalent binding to the active site cysteine. These potent GSTO1 inhibitors suppress cancer cell growth, enhance the cytotoxic effects of cisplatin, and inhibit tumor growth in colon cancer models as single agent. Bru-seq-based transcription profiling unraveled novel roles for GSTO1 in cholesterol metabolism, oxidative and endoplasmic stress responses, cytoskeleton, and cell migration. Our findings demonstrate the therapeutic utility of GSTO1 inhibitors as anticancer agents and identify novel cellular pathways under GSTO1 regulation in colorectal cancer.
Project description:Global analyses on gene expression profiles in two soybean species, Nanahomare and Tamahomare was performed using DNA microarray technique. Nanahomare is glycinin deficient species, and is high in free amino acid content. Tamahomare is parent species of Nanahomare. In Nanahomare, stress related genes glutathione S-transferase and ascorbate peroxidase had higher expression than in Tamahomare, which suggests glycinin-deficiency caused stress in soy seeds, and that it lead Nanahomare to increase in free amino acid content. Keywords: storage protein deficiency
Project description:The core promoter of protein-encoding genes plays a central role in regulating transcription. M1BP is a transcriptional activator that associates with a core promoter element known as Motif 1 that resides at thousand of genes in Drosophila. To gain insight into how M1BP functions, we identified an interacting protein called GFZF. GFZF had been previously identified in genetic screens for factors involved in maintenance of hybrid inviability, the G2-M DNA damage checkpoint, and RAS/MAPK signaling but its contribution to these processes was unknown. Previous evidence indicated that GFZF resides in the cytoplasm. Here, we show that GFZF resides in the nucleus and functions as a transcriptional co-activator. In addition, we show that GFZF is a glutathione S-transferase(GST). Thus, GFZF is the first transcriptional co-activator with intrinsic GST activity, and its identification as a transcriptional co-activator provides an explanation for its role in numerous biological processes.
Project description:Whilst M. bovis Bacillus Calmette-Guérin (BCG) therapy remains the gold-standard for treatment of high-risk non-muscle invasive bladder cancer (BC), 30-40% of patients fail therapy, resulting in disease recurrence and progression. Loss of glutathione-S-transferase theta 2 (GSTT2) expression has been associated with improved response to fewer instillations of BCG. To understand these responses, wild-type (WT) and GSTT2-knockout (KO) mice were implanted orthotopically with MB49-PSA BC cells, and mice were treated with four weekly BCG instillations, after which the bladders were harvested for single-cell RNA sequencing.
Project description:Background: Lactobacillus plantarum is found in a variety of fermented foods and as such, consumed for centuries. Some strains are natural inhabitants of the human gastro-intestinal tract and like other Lactobacillus species, L. plantarum has been extensively studied for its immunomodulatory properties and its putative health-promoting effects (probiotic). Being the first line of host defense intestinal epithelial cells (IEC) are key players in the recognition and initiation of responses to gut microorganisms. Results: Using high-density oligonucleotide microarrays we examined the gene expression profiles of differentiated Caco-2 cells exposed to various doses of L. plantarum. In addition, the effects were correlated to monolayer permeability studies and measurement of lactic acid production. A transcriptional dose-dependent IEC response to L. plantarum was found. Incubation of Caco-2 with a low bacterial dose induced a specific response, not due to cytotoxicity or production of lactic acid, including modulation of cell cycle and cell signaling functions. Exposure of Caco-2 cells to larger amounts of bacteria, accompanied by the production of lactic acid and glucose depletion, provoked increased permeability and supposed non-specific defense responses. Conclusions: These results suggest that IEC are able to sense and react to the presence of gut bacteria. This study provides the first description of global transcriptional response of human IEC to a commensal lactic acid bacterium, and it shows the importance of choosing physiological bacterial doses to prevent the observation of non-specific host reactions. Caco-2 cells were exposed for 10h to Lactobacillus. Fourteen samples are analyzed: 4 control Caco-2, 4 Caco-2 exposed to a low dose (10) of Lactobacillus, 4 Caco-2 exposed to a medium dose (100) of Lactobacillus, 2 Caco-2 exposed to a high dose (1000) of Lactobacillus. All 14 RNA samples are labeled with Cy5 and hybridized to a common reference (undifferentiated Caco-2, untreated) RNA labeled with Cy3
Project description:In this study, we examined Caco-2 cell gene expression after infection with E. coli (Ec), Lactobacillus plantarum (Lp) and the combination of the two (mix) Keywords: Lactobacillus plantarum and E. coli influences on Caco2 cells gene expression
