Impact of Dichlorvos on Expression of Superoxide Dismutase in
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ABSTRACT:
PROVIDER: PRJEB96396 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Oxidative stress is a key contributor to the development of dysregulated inflammation in acute lung injury (ALI). A naturally occurring single nucleotide polymorphism in the key extracellular antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), results in an arginine to glycine substitution (R213G) which promotes resolution of inflammation and protection against bleomycin-induced ALI. Previously we found that mice with the R213G mutation in EC-SOD have an inflammation-resolving transcriptomic profile at 7 days post-bleomycin However, the epigenetic differences between WT and R213G EC-SOD lungs have not been examined. Therefore, we used Next Generation microRNA (miR) Sequencing of lung tissue to identify dysregulated miRs 7 days after bleomycin in wild-type (WT) and R213G mice. Methods: WT and homozygous R213G EC-SOD (rs1799895) mice received one intratracheal administration of bleomycin in phosphate-buffered saline (PBS) (100 uL at 1 U/mL) or PBS at 8-12 weeks old. Lungs were harvested and frozen. Frozen lungs were homogenized, placed in Qiazol, and RNA was isolated using the miRNeasy Mini Kit (Qiagen). Samples underwent 1x150, directional, single-end sequencing using the Illumina hiSEQ 4000 system. Results: 1424 microRNAs were detected. Up/Down regulated microRNAs were defined as havinga FC > 1.2 and p <0.05. microRNAs "unique" to a genotype were defined as meeting the prevoius criteria in only one strain, or in both with a fold change 1.5x greater in one over the other. This method identified 92 WT and 235 R213G miRs uniquely dysregulated in their respective genotypes.
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Project description:The proteins are a pair of closely related superoxide dismutase (SOD) enzymes from the Gram positive bacterium, Staphylococcus aureus. SodA is a Mn-specific SOD (MnSOD), which is inactive when loaded with Fe, whereas SodM is a 'cambialistic' SOD (camSOD), which is catalytically active with either Mn or Fe as a cofactor. Their sequences are 75% identical across their 199 amino acid sequences: the crystal structures of each enzyme in each metal-loaded form: Mn-loaded MnSOD SodA: PDB ID 5N56 Fe-loaded MnSOD SodA: PDB ID 6EX3 Mn-loaded camSOD SodM: PDB ID 5N57 Fe-loaded camSOD SodM: PDB ID 6EX4 The resulting structures (all to approximately 2A resolution) showed no significant differences that indicated molecular reasons for the differences in activity. Because of the differences in activity, therefore, the project aimed to compare three forms of these enzymes to determine whether there are any differences in the dynamics of regions of their structure, most notably those within the active site and the putative substrate access route(s).
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Project description:Sepsis-induced liver injury is an important cause of septicemia deaths, this injury is characterized by an overproduction of reactive oxygen species (ROS) within the liver, which activates the inflammatory response and results in the release of numerous inflammatory factors, ultimately leading to liver damage. Thus, the development of medicines capable of eliminating ROS and reducing inflammatory factors holds significant prospects. In this study, we synthesized and characterized a natural superoxide dismutase-mimicking carbon dots (G-CDs) form a greenery Glycyrrhiza with distinctive ROS scavenging ability for SILI therapy. The abundant surface unsaturated groups especially oxhydry and carbonyl groups enable G-CDs to exhibit excellent SOD-like enzyme activity exceeding 10000 U/mg and significantly reduce the excessive production of ROS and inflammatory factors. In addition, G-CDs reduced inflammation, oxidative damage, and tissue damage in the liver of lipopolysaccharide (LPS) induced SILI mice model. Mechanistically, G-CDs protect liver tissue by activating Keap-1/Nrf-2 mediated antioxidant signaling and inhibiting NF-κB-dependent inflammatory responses. In conclusion, this study establishes the potential of G-CDs as a promising therapeutic agent for the treatment SILI.
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Project description:The importance of manganese superoxide dismutase (Mn-SOD), an evolutionarily ancient metalloenzyme maintaining the integrity and functions of mitochondria, was studied in oxidative stress treated Aspergillus fumigatus cultures. Deletion of the Mn-SOD gene (sodB) increased both the menadione sodium bisulfite (MSB) elicited oxidative stress, and the deferiprone (DFP) induced iron limitation stress sensitivity of the strain. Moreover, DFP treatment enhanced the MSB sensitivity of both the gene deletion mutant and the reference strain. Concurring with these results, RNS sequencing data also demonstrated that deletion of sodB largely altered the MSB induced oxidative stress response. The difference between the oxidative stress responses of the two strains manifested mainly in the intensity of the response. Importantly, upregulation of “Ribosome protein”, “Iron uptake”, and Fe-S cluster assembly” genes, alterations in the transcription of “Fe-S cluster protein” genes, downregulation of “Heme binding protein” genes under MSB stress were characteristic for only the DsodB gene deletion mutant. We assume that the elevated superoxide level generated by MSB treatment may have destroyed Fe-S cluster proteins of mitochondria in the absence of SodB mediated protection. Re-synthesis of Fe-S cluster proteins enhanced translation and increased iron demand changing iron metabolism and increasing DFP sensitivity considerably.
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Project description:Rotifers are useful model organisms for aging research, owing to their small body size (0.1-1 mm), short lifespan (6-14 days) and the relative easy in which aging and senescence phenotypes can be measured. Recent studies have shown that antioxidants can extend the lifespan of rotifers. In this paper, we analyzed changes in the mRNA expression level of genes encoding the antioxidants manganese superoxide dismutase (MnSOD), copper and zinc SOD (CuZnSOD) and catalase (CAT) during rotifer aging to clarify the function of these enzymes in this process. We also investigated the effects of common life-prolonging methods [dietary restriction (DR) and resveratrol] on the mRNA expression level of these genes. The results showed that the mRNA expression level of MnSOD decreased with aging, whereas that of CuZnSOD increased. The mRNA expression of CAT did not change significantly. This suggests that the ability to eliminate reactive oxygen species (ROS) in the mitochondria reduces with aging, thus aggravating the damaging effect of ROS on the mitochondria. DR significantly increased the mRNA expression level of MnSOD, CuZnSOD and CAT, which might explain why DR is able to extend rotifer lifespan. Although resveratrol also increased the mRNA expression level of MnSOD, it had significant inhibitory effects on the mRNA expression of CuZnSOD and CAT. In short, mRNA expression levels of CAT, MnSOD and CuZnSOD are likely to reflect the ability of mitochondria to eliminate ROS and delay the aging process.
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