Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA115869 | ENA |
REPOSITORIES: ENA
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Project description:Superoxide radical anion and other Reactive Oxygen Species are constantly produced during respiration. In mitochondria, the dismutation of the superoxide radical anion is accelerated by the mitochondrial superoxide dismutase 2 (SOD2), an enzyme that has been traditionally associated with antioxidant protection. However, increases in SOD2 expression promote oxidative stress, indicating that there may be a prooxidant role for SOD2. We show that SOD2, which normally binds manganese, can incorporate iron and generate an alternative isoform with peroxidase activity. The switch from manganese to iron allows FeSOD2 to utilize H2O2 to promote oxidative stress. We found that FeSOD2 is formed in cultured cells. FeSOD2 causes mitochondrial dysfunction and higher levels of oxidative stress in cultured cells. We show that formation of FeSOD2 converts an antioxidant defense into a prooxidant peroxidase that leads to cellular changes seen in multiple human diseases.
2017-12-05 | GSE106206 | GEO
Project description:Global Gene Expression Analysis Reveals Differences in Cellular Responses to Hydroxyl- and Superoxide-induced Oxidative Stress in Caco-2 Cells. Reactive oxygen species-induced oxidative stress in the colon is involved in inflammatory bowel diseases and is suggested to be associated with colorectal cancer risk. However, our insight in molecular responses to different oxygen radicals is still fragmentary. Therefore, we studied global gene expression by an extensive time serie (0.08, 0.25, 0.5, 1, 2, 4, 8, 16, or 24 hours ) analyses in human colon cancer (Caco-2) cells after exposure to H2O2 or menadione, leading to the formation of HO. or O2.- radicals respectively. Next to gene expression, induction of pathways and correlations with related phenotypic markers (oxidative DNA damage, cell cycle arrest) was investigated. Gene expression analysis resulted in 1404 differentially expressed genes upon H2O2 challenge and 979 genes after menadione treatment. Time-dependent co-regulated genes immediately showed a pulse-like response to HO. formation while the O2.--induced expression is not restored over 24 hours. Pathway analyses demonstrated that the difference in the modulation of gene expression is also reflected in regulation of pathways by HO. and O2.-: H2O2 immediately influences pathways involved in the immune function, while menadione constantly regulated cell cycle-related pathways. Altogether, this study offers a novel and detailed insight in differential time-dependent oxidative stress response, but most importantly, shows that effects of HO. and O2.- can also be discriminated regarding their modulation of particular carcinogenesis-related mechanisms. Keywords: Comparison of genome-wide gene expression between different time points for H2O2 and menadione.
2010-01-12 | GSE15327 | GEO
Project description:RNA solvent accessibility by hydroxyl radical probing
| PRJNA802981 | ENA
Project description:Investigation of whole genome gene expression level changes in Arabidopsis roots by the effect of light. Plant growth is sustained by a continuous cell division in meristems followed by cell differentiation and elongation. We have found that in Arabidopsis thaliana roots, flavonols play a key role in regulating the transition from cell division to differentiation. Using an engineered device to grow roots in darkness, but shoot in light cycle, coupled with transcriptomic and metabolomics analysis, we deciphered that flavonols accumulation regulates proliferation-promoting levels of auxin-PLETHORA and superoxide anion (O2-). High flavonols levels restrict auxin transport and the PLETHORA gradient but also superoxide radical content, promoting an accelerated cell differentiation. Furthermore, cytokinin-SHY2 and H2O2-UPB1 pathways, which promote differentiation and, respectively, antagonize auxin and O2- activity, increase flavonols biosynthesis establishing mutual interactions among these pathways. Flavonols function as positional signals integrating hormonal and ROS pathways to determine final organ growth. This work analyze the effect of root illumination in gene transcription. Details of how plants and roots are grown are described in Silva et al. (submitted)
2016-04-01 | GSE68093 | GEO
Project description:Investigation of whole genome gene expression level changes in Arabidopsis roots by the effect of light. Plant growth is sustained by a continuous cell division in meristems followed by cell differentiation and elongation. We have found that in Arabidopsis thaliana roots, flavonols play a key role in regulating the transition from cell division to differentiation. Using an engineered device to grow roots in darkness, but shoot in light cycle, coupled with transcriptomic and metabolomics analysis, we deciphered that flavonols accumulation regulates proliferation-promoting levels of auxin-PLETHORA and superoxide anion (O2-). High flavonols levels restrict auxin transport and the PLETHORA gradient but also superoxide radical content, promoting an accelerated cell differentiation. Furthermore, cytokinin-SHY2 and H2O2-UPB1 pathways, which promote differentiation and, respectively, antagonize auxin and O2- activity, increase flavonols biosynthesis establishing mutual interactions among these pathways. Flavonols function as positional signals integrating hormonal and ROS pathways to determine final organ growth. This work analyze the effect of root illumination in gene transcription. Details of how plants and roots are grown are described in Silva et al. (submitted) A six chip study using total RNA extracted from three independent experiments of Arabidopsis roots growing in presence of light and three independent experiments of Arabidopsis roots growing without light.
2016-04-01 | E-GEOD-68093 | biostudies-arrayexpress
Project description:Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysteriouss. Therefore, investigating the function of superoxide anion, the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of superoxide anion changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for superoxide anion and HSCs targeting peptides. We observe that superoxide anion in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by superoxide anion, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.
2024-04-08 | PXD051328 |
Project description:Mutations in the Microrchidia CW-Type Zinc Finger 2 (MORC2) GHKL ATPase module cause Charcot Marie Tooth type 2Z or a broad range of neuropathy, but etiology and therapeutic strategy are not fully defined. Previously, we reported that the Morc2a p.S87L mouse model led to neuropathy and muscular dysfunction through DNA damage accumulation. This study revealed that Morc2a p.S87L caused a protein synthesis defect, resulting in the loss of function of Morc2a and weakening its function of maintaining DNA integrity and hydroxyl radical scavenging in the GHKL ATPase domain. Morc2a GHKL ATPase domain was considered a therapeutic target based on its function of simultaneously complementing hydroxyl radical scavenging and ATPase activity. Adeno-associated virus PHP.eB serotype that has high central nervous system transduction efficiency was applied to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. AAV gene therapy improved neuropathy and muscular dysfunction with single-time treatment. The loss of function characteristics due to protein synthesis defect in Morc2a p.S87L was also observed in human MORC2 p.S87L or p.R252W variant, suggesting a relevance between mouse and human pathogenesis. Here, we demonstrate Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy and could be rescued through AAV-based gene therapy.
2024-02-06 | GSE235918 | GEO
Project description:Directed hydroxyl radical probing reveals Upf1 binds 80S ribosomal E site rRNA at L1 stalk
| PRJNA408153 | ENA
Project description:High resolution-hydroxyl radical protein footprinting LC-MS/MS files of NRG1-Ig like domain.
2022-03-30 | MSV000089169 | MassIVE