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Query: EC:3.4.11.18 (MAP)
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Epidemiological studies suggest that dietary phytosterols may offer protection form some types of cancer including breast cancer. In an attempt to investigate the mechanism by which phytosterols offer this protection, we investigated the effect of the two most common dietary phytosterols, beta-sitosterol and campesterol, on the mevalonate and MAP Kinase (MAPK) pathways in MDA-MB-231 cells. These pathways play a role in cell growth and apoptosis. MDA-MB-231 cell line was used in this study since it is a hormone-insensitive tumor cell line which represents the majority of advanced breast cancer cases. Cells grown in the presence of 16 microM beta-sitosterol or campesterol for 3 days exhibited a 70% and 6% reduction in cell growth, respectively, while cholesterol treatment had no effect on growth as compared to the control. Studies investigating the effect of sterol supplementation on the relative and total sterol composition of cells, showed that cells supplemented with cholesterol contained 23% more cholesterol than the control. Cells supplemented with campesterol had almost one-half the cholesterol of controls but accumulated campesterol to account for 40% of the total sterols. In the case of cells supplemented with beta-sitosterol, cells had only 25% of their sterols as cholesterol and the rest was in the form of beta-sitosterol. All sterols tested equally inhibited de novo cholesterol synthesis using 14C-acetate as substrate. beta-Sitosterol supplemented cells had reduced cholesterol synthesis when using 3H-mevalonolactone as substrate, which suggests that the inhibition in this pathway is downstream of mevalonate where processes such as isoprenylation of proteins may take place. Mevalonate supplementation to cells treated with beta-sitosterol did not completely correct the observed growth inhibition by beta-sitosterol. There was no effect of sterols on the concentrations of both low (21-26 kDa) or high (44-74 kDa) molecular weight isoprenylated proteins in these cells. On the other hand, both the quantity and activity of MAPK was elevated in the cells supplemented with beta-sitosterol. These data suggest that the down regulation of cholesterol synthesis from mevalonate and stimulation of the MAPK pathway may play roles in the inhibition of MDA-MB-231 cell growth by beta-sitosterol.
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PMID:Effect of phytosterols on cholesterol metabolism and MAP kinase in MDA-MB-231 human breast cancer cells. 1266 3

As a consequence of global climate change, certain stress factors that have a negative impact on crop productivity such as heat, cold, drought and salinity are becoming increasingly prevalent. We conducted a meta-analysis to identify genes conserved across plant species involved in (1) general abiotic stress conditions, and (2) specific and unique abiotic stress factors (drought, salinity, extreme temperature) in leaf tissues. We collected raw data and re-analysed eight RNA-Seq studies using our previously published bioinformatic pipeline. A total of 68 samples were analysed. Gene set enrichment analysis was performed using MapMan and PageMan whereas DAVID (Database for Annotation, Visualisation and Integrated Discovery) was used for metabolic process enrichment analysis. We identified of a total of 5122 differentially expressed genes when considering all abiotic stresses (3895 were upregulated and 1227 were downregulated). Jasmonate-related genes were more commonly upregulated by drought, whereas gibberellin downregulation was a key signal for drought and heat. In contrast, cold stress clearly upregulated genes involved in ABA (abscisic acid), cytokinin and gibberellins. A gene (non-phototrophic hypocotyl) involved in IAA (indoleacetic acid) response was induced by heat. Regarding secondary metabolism, as expected, MVA pathway (mevalonate pathway), terpenoids and alkaloids were generally upregulated by all different stresses. However, flavonoids, lignin and lignans were more repressed by heat (cinnamoyl coA reductase 1 and isopentenyl pyrophosphatase). Cold stress drastically modulated genes involved in terpenoid and alkaloids. Relating to transcription factors, AP2-EREBP, MADS-box, WRKY22, MYB, homoebox genes members were significantly modulated by drought stress whereas cold stress enhanced AP2-EREBPs, bZIP members, MYB7, BELL 1 and one bHLH member. C2C2-CO-LIKE, MADS-box and a homeobox (HOMEOBOX3) were mostly repressed in response to heat. Gene set enrichment analysis showed that ubiquitin-mediated protein degradation was enhanced by heat, which unexpectedly repressed glutaredoxin genes. Cold stress mostly upregulated MAP kinases (mitogen-activated protein kinase). Findings of this work will allow the identification of new molecular markers conserved across crops linked to major genes involved in quantitative agronomic traits affected by different abiotic stress.
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PMID:Identification of conserved genes linked to responses to abiotic stresses in leaves among different plant species. 3272 52