Benefits of whole grains as dietary supplements and active ingredients in health products have been promoted. Despite being neglected as an agricultural byproduct of polished rice, pigmented rice bran has emerged as a promising source of natural anti-aging compounds. Indeed, the extract of red rice bran Hom Dang cultivar contained rich phenolic acids and flavonoids. It displayed high antioxidant activities in vitro and in vivo assays. Using yeast model, extract and bioactive compounds, quercetin and protocatechuic acid found in the rice bran pericarp, effectively reduced levels of intracellular reactive oxygen species (ROS), restored plasma membrane damages and prolonged life-span of pre-treated wild-yeast cells. Importantly, these molecules modulated life span-extension through a mechanism of ROS reduction that resembles to that operated under the highly conserved Tor1- and Sir2-dependent signaling pathways, with the human homologs TORC1 and SIRT1, respectively. The key longevity factors Sch9 and Rim15 kinases, Msn2/4 regulators and a novel transcription factor Asg1, the antioxidant enzymes superoxide dismutases and glutathione peroxidases played important role in mediating longevity. Yeast clearly provides an instrumental platform for rapid screening of compounds with anti-aging efficacies and advances knowledge in the molecular study of ageing.
In this study, we characterize a new function for activator of stress response genes (Asg1) in fatty acid utilization. Asg1 is required for full activation of genes in several pathways, including β-oxidation (POX1, FOX2, and POT1), gluconeogenesis (PCK1), glyoxylate cycle (ICL1), triacylglycerol breakdown (TGL3), and peroxisomal transport (PXA1). In addition, the transcriptional activator Asg1 is found to be enriched on promoters of genes in β-oxidation and gluconeogenesis pathways, suggesting that Asg1 is directly involved in the control of fatty acid utilizing genes. In agreement, impaired growth on non-fermentable carbons such as fatty acids and oils and increased sensitivity to some oxidative agents are found for the Δasg1 strain. The lipid class profile of the Δasg1 cells grown in oleate displays approximately 3-fold increase in free fatty acid (FFA) content in comparison to glucose-grown cells, which correlates with decreased expression of β-oxidation genes. The ∆asg1 strain grown in glucose also exhibits higher accumulation of triacylglycerols (TAGs) during log phase, reaching levels typically observed in stationary phase cells. Altered TAG accumulation is partly due to the inability of the Δasg1 cells to efficiently break down TAGs, which is consistent with lowered expression of TGL3 gene, encoding triglycerol lipase. Overall, these results highlight a new role of the transcriptional regulator Asg1 in coordinating expression of genes involved in fatty acid utilization and its role in regulating cellular lipid accumulation, thereby providing an attractive approach to increase FFAs and TAGs content for the production of lipid-derived biofuels and chemicals in Saccharomyces cerevisiae.
Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ’s transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.
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