Molecular mechanisms of lifespan extension in long-lived mitocondrial superoxide dismutase sod-2 mutants
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE286219 | GEO | 2025/02/25
REPOSITORIES: GEO
Similar Datasets
Project description:Molecular mechanisms of lifespan extension in long-lived mitocondrial superoxide dismutase sod-2 mutants
| PRJNA1208437 | ENA
Project description:isp-1;sod double mutants have decreased lifespan, increased resistance to oxidative stress and slow physiologic rates. We performed RNA sequencing to compare gene expression between isp-1 mutants and isp-1;sod-3 and isp-1;sod-5 double mutants
2017-08-30 | GSE95240 | GEO
Project description:The C. elegans nervous system mediates protective physiological and behavioral responses amid infection. However, it remains largely unknown how the nervous system responds to reactive oxygen species (ROS) activated by pathogenic microbes during infection. Here, we show superoxide dismutase-1 (SOD-1), an enzyme that converts superoxide into less toxic hydrogen peroxide and oxygen, functions in the gustatory neuron ASER to mediate C. elegans pathogen avoidance response. When C. elegans first encounters pathogenic bacteria P. aeruginosa, SOD-1 is induced in the ASER neuron. After prolonged P. aeruginosa exposure, ASER-specific SOD-1 expression is diminished. In turn, C. elegans starts to vacate the pathogenic bacteria lawn. Genetic knockdown experiments reveal that pathogen-induced ROS activate sod-1 dependent behavioral response non cell-autonomously. We postulate that the delayed aversive response to detrimental microbes may provide survival benefits by allowing C. elegans to temporarily utilize food that is tainted with pathogens as an additional energy source. Our data offer a mechanistic insight into how the nervous system mediates food-seeking behavior amid oxidative stress and suggest that the internal state of redox homeostasis could underlie the behavioral response to harmful microbial species.
| S-EPMC5359715 | biostudies-literature
Project description:The scavenging of reactive oxygen species (ROS) within cells is regulated by several interacting factors, including transcriptional regulators. Involvement of sarA family genes in the regulation of proteins involved in the scavenging of ROS is largely unknown. In this report, we show that under aerobic conditions, the levels of sodM and sodA transcription, in particular the sodM transcript, are markedly enhanced in the sarA mutant among the tested sarA family mutants. Increased levels of sod expression returned to near the parental level in a single-copy sarA complemented strain. Under microaerophilc conditions, transcription of both sodM and sodA was considerably enhanced in the sarA mutant compared to the wild-type strain. Various genotypic, phenotypic, and DNA binding studies confirmed the involvement of SarA in the regulation of sod transcripts in different strains of Staphylococcus aureus. The sodA mutant was sensitive to an oxidative stress-inducing agent, methyl viologen, but the sarA sodA double mutant was more resistant to the same stressor than the single sodA mutant. These results suggest that overexpression of SodM, which occurs in the sarA background, can rescue the methyl viologen-sensitive phenotype observed in the absence of the sodA gene. Analysis with various oxidative stress-inducing agents indicates that SarA may play a greater role in modulating oxidative stress resistance in S. aureus. This is the first report that demonstrates the direct involvement of a regulatory protein (SarA) in control of sod expression in S. aureus.
| S-EPMC2687179 | biostudies-literature
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.
2025-01-01 | GSE269970 | GEO
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.
2020-05-29 | GSE147138 | GEO
Project description:In the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM-remodeling and left ventricular (LV) dysfunction. This study aimed to evaluate the effects of CatA overexpression on LV remodeling. A proteomic analysis of the secretome of adult mouse cardiac fibroblasts upon digestion by CatA identified the extracellular antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate of CatA (5-fold decreased abundance; p=0.0001). In vitro, cardiomyocytes and cardiac fibroblasts expressed and secreted CatA protein. EC-SOD protein was expressed and secreted only by cardiac fibroblasts. Cardiomyocyte-specific over-expression of CatA and increased activity in the LV of transgenic mice (CatA-TG) reduced EC-SOD protein levels by 43% (p<0.001). Loss of EC-SOD-mediated anti-oxidative protection resulted in accumulation of superoxide radicals (WT: 4.54±1.2 vs. CatA-TG: 8.62±2.3µmol/mg tissue/min; p=0.0012), increased inflammation, myocyte hypertrophy (WT: 19.8±1.0 vs. CatA-TG: 21.9±1.8µm; p=0.024), cellular apoptosis, and elevated mRNA expression of hypertrophy-related and pro-fibrotic marker genes, without effecting intracellular detoxifying proteins. In CatA-TG mice LV interstitial fibrosis formation was enhanced by 19% (p=0.028) and type I/type III collagen ratio was shifted towards higher abundance of collagen I fibers (p=0.026). Cardiac remodeling in CatA-TG was accompanied by increased LV weight/body weight and LV enddiastolic volume (WT: 50.8±5.8 vs. CatA-TG: 61.9±6.2 µl; p=0.018). Thus, in the heart CatA-mediated reduction of EC-SOD protein contributes to increased oxidative stress, myocyte hypertrophy, ECM remodeling and inflammation. This implicates CatA as a potential therapeutic target to prevent ventricular remodeling.
2020-07-10 | PXD019895 | Pride
Project description:The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants-including slow development, low brood size, and slow defecation-this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function.
| S-EPMC2628729 | biostudies-literature
Project description:Superoxide dismutase (SOD) is an essential enzyme of the plant antioxidant system that responds to oxidative damage caused by adverse conditions. However, little is known about the SOD gene family in Vitis vinifera (Vv). In the present study, ten SOD genes, including 6 copper/zinc SODs, 2 iron SODs, and 2 manganese SODs, were identified in the grapevine genome where they were unevenly distributed on 12 chromosomes. Ten VvSOD genes were divided into three main groups based on phylogenetic analysis, subcellular localization, and the distribution of conserved protein motifs. Additionally, many cis-elements related to different stresses were found in the promoters of the 10 VvSOD genes. Syntenic analysis revealed that VvMSD1 and VvMSD2 were derived from segmental duplication, and VvCSD4 and VvCSD5 belong to a pair of tandemly duplicated genes. Gene expression analysis based on microarray data showed that the 10 VvSOD genes were expressed in all the tested tissues. Interestingly, the segmentally duplicated gene pair (VvMSD1 and VvMSD2) exhibited differential expression patterns in various organs. In contrast, the tandemly duplicated gene pair (VvCSD4 and VvCSD5) displayed similar expression patterns in the tested organs. Our results provide a basis for further functional research on the SOD gene family in grapevine.
| S-EPMC6409070 | biostudies-literature
Project description:PurposeSuperoxide dismutase (SOD) is an important component of antioxidative defense systems and plays an important role in protecting spermatozoa from oxidative damage. In this study, we assessed seminal SOD activity, its association with semen parameters, and also genetic and non-genetic factors contributing to the determination of SOD activity in infertile men.MethodsSemen samples were obtained from 435 male infertility patients. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay. Four single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 genes were genotyped using OpenArray platform.ResultsWe found that seminal SOD activity was positively associated with sperm concentration and overall motility, whereas inversely with sperm DNA fragmentation. In addition, infertile men with SOD2 rs4880 CC variants showed a low level of SOD activity when compared with TT carriers (Mean ± SD: 268.3 ± 102.3 and 342.8 ± 98.2, respectively, P = 0.005). Those who consumed vitamin C/E (≥3 times per week) had a significantly higher SOD activity level than those who did not (mean ± SD: 379.8 ± 93.3 and 332.2 ± 94.9, respectively, P = 0.001).ConclusionsSeminal SOD activity and other factors influencing SOD activity play a role in determining sperm fertilization potential and male infertility.
| S-EPMC4016371 | biostudies-literature