Metabolic Regulation Mechanism Of Copper Ion On Saccharomyces Cerevisiae Under Paraquat Stress

Paraquat is a non-selective herbicide with strong toxicity to humans and mammals.However,the proteome regulation of cells by paraquat is still unclear,limiting the development of antidotes.Studies have shown that a slight excess of intracellular levels of copper could be beneficial to the survival under exposure to paraquat.In this study,Saccharomyces cerevisiae was used as a model to explore bacterial protein expression and metabolic network regulation mechanisms by the approach of high-throughput proteomics and intracellular metabolomics.So as to analyze and evaluate the toxicity of paraquat on cells and the regulation effect of copper ion on paraquat poisoning.The results showed that the stress of paraquat caused the accumulation of free radicals in mitochondria,which in turn damaged cell structure and function.The channels for cells to absorb external nutrients were blocked,and the overactivity of ribosomal biogenesis accelerated intracellular metabolism,causing the down-regulation of key metabolic intermediates in the main energy cycle of mitochondria,resulting in decreased cell resistance.The oxidative stress of paraquat also causes gene expression disorders,cytotoxicity,increased cellular inflammation and risk of cell malignant proliferation,thereby promoting cell senescence and death.The pre-incubation of 0.2 m M of Cu²⁺involved a series of favorable reactions to cell survival under paraquat stress.That mainly include activation of mitogen-activated protein kinase signal transduction pathway to maintain cell wall integrity and normal cell growth.Regulation of heme,steroid biosynthesis pathway,sulfur assimilation pathway and carbon metabolism pathway to generate heme,ergosterol,sulfide and glutathione and other antioxidants.Upregulating expression of cellular stress resistance genes and metallothionein.Antioxidant molecules and stress resistance genes together constitute detoxification system of cells to resist oxidative damage.The pre-incubation of Cu²⁺also repaired DNA damage and ensured the stability of the gene expression process.The cellular inflammatory response caused by paraquat was reliefed,the content of harmful molecules in the cell was reduced to protect the cell from the toxicity of paraquat.These findings inferred that 0.2 m M of Cu²⁺could prolong the survival of cells under paraquat stress.