Project description:The present study aimed at proposing a novel chemically-induced cirrhosis-associated rat hepatocarcinogenesis model, involving the characterization of histological, biochemical and molecular features. Male Wistar rats received a single dose of diethylnitrosamine (DEN, 200 mg/Kg body weight [b.wt.]), and were submitted to several cycles of thioacetamide (TAA, 200 mg/Kg b.wt.), during 23 weeks. Blood and liver were collected from untreated and DEN/TAA-treated groups. Liver samples were processed for global gene expression (cDNA microarray), histopathological (HE) and collagen content (picrosirius red) evaluations, immunohistochemical (Ki-67, GST-P and α-SMA), biochemical (catalase, glutathione peroxidase and glutathione-S-transferase) and gelatin zymography (MMP-2 and 9) analysis. Using a very stringent analysis (FDR<0.01 and fold change>3), gene expression array evidenced 359 differentially expressed genes upon DEN/TAA regimen. Gene Ontology and functional analyses showed several upregulated genes involved in extracellular matrix organization, mainly collagen type I α1 and 2 (Col1α1, Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 (Timp1 and Timp2) genes. In addition, glutathione S-transferase, pi 1 and 2 (Gstp1 and Gstp2) genes were markedly upregulated. In contrast, functional analyses also revealed the downregulation of antioxidant response genes, as catalase, glutathione peroxidase 1 and glutathione S-transferase mu type 3 (Cat, Gpx1 and Gstm3). In agreement with gene expression data, our model presented extensive liver cirrhosis with increased α-SMA expression and collagen deposition, as well as marked development of preneoplastic GST-P positive hyperplastic lesions and some neoplasms. Besides, we observed a decrease in total glutathione peroxidase, total glutatione-S-tranferase and catalase activities. The characterization of a suitable cirrhosis-associated hepatocarcinogenesis model could provide insights into molecular characteristics of the human disease and be applied to evaluate potential preventive and therapeutic approaches.
Project description:Native protein extracts from 2-week-old seedlings of wild-type and GPX1-OE lines were used to identify interactions partners of glutathione peroxidase 1 in rice.
Project description:Mulberry (Morus alba) is a fast-growing perennial woody plant with a long cultivation history in China and a distribution throughout the country. To date, the molecular mechanism of mulberry response to abiotic stress is little known. In the present study, proteomics data were collected from the leaves of the mulberry cultivar Neo-Ichinose (Japan) under drought stress and analyzed. In total, 2871 proteins were quantified, among which 267 proteins were differentially expressed. A Gene Ontology enrichment analysis indicated that the molecular functions of the up-regulated proteins were mainly related to glutathione peroxidase activity, hydrolase activity, oxidoreductase activity, peroxidase activity and antioxidant activity. Protein domain enrichment analysis showed that the most important protein domains were associated with glutathione peroxidase, glycoside hydrolase, and chaperones. Additionally, a functional enrichment analysis demonstrated that the main metabolic pathways of mulberry seedlings in response to drought stress were arachidonic acid metabolism and glutathione metabolism, which were up-regulated, and chlorophyll and porphyrin metabolism and glycerol metabolism, which were down-regulated. Additionally, many proteins related to osmotic adjustment and stress signal transduction were evoked by drought. Taken together, these results suggested that redox control and osmotic adjustment mediated by multiple signaling pathways dominated the drought response of mulberry and that antioxidant proteins and enzymes, especially glutathione peroxidase, played vital roles in the redox rebalance of mulberry under stress.
2022-10-13 | PXD010227 | Pride
Project description:Maize rotation combined with Streptomyces rochei D74 to eliminate Orobanche cumana seed bank in the farmland
Project description:We reported glutathione peroxidase-1 (GPx1) was negatively associated with overall survival in pancreatic ductal adenocarcinoma patients. Silencing GPx1 in pancreatic cancer cells showed epithelial–mesenchymal transition phenotype and increased chemoresistance to gemcitabine in vitro and in vivo. Next, to search for a putative molecular mechanism, we used a high-throughput gene expression profiling array in scramble-shRNA and GPx1-shRNA pancreatic cancer cells (MiaPaCa-2). This study provides the differentially expressed genes and altered signaling pathways towards characterization of gemcitabine resistance cell populations.
Project description:Polyunsaturated fatty acids (PUFA) sensitize cells to ferroptotic cell death. In the study associated with this dataset, we used UACC257 as a model cell line (intrinsically resistant to ferroptosis) induced to be sensitive to ferroptosis with different PUFAs. We performed genome-wide CRISPR knockout screen to identify genes that mediate the sensitivity to ML210, a selective inhibitor of glutathione peroxidase 4 (GPX4) and a potent inducer of ferroptotic cell death. We identified cytochrome P450 oxidoreductase (POR, CYPOR) as a key player required for ferroptotic cell death among other genes.
Project description:To address the hypothesis that silencing deleterious or protective injury-induced genes in the rat hippocampus will reduce or increase the numbers of injured hippocampal neurons, alter cellular pathways essential for neuronal function and improve or worsen functional outcome after traumatic brain injury (TBI), we evaluated the effects of silencing neuronal nitric oxide synthase (nNOS) and glutathione peroxidase-1 (GPx-1) expression in the injured rat hippocampus.