Ferroptosis and Neurodegenerative Diseases: Insights into the Regulatory Roles of SLC7A11

Wang, Chen; Liu, Haihui; Xu, Si; Deng, Yu; Xu, Bin; Yang, Tianyao; Liu, Wei

doi:10.1007/s10571-023-01343-7

Cited by 12 publications

(5 citation statements)

References 179 publications

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“…At the same time, both drugs are also found to down-regulate the expression of the amino acid transporter SLC7A11. SLC7A11 knockout mice also have an increased bleeding time phenotype (MP:0005606), and mutations in this gene have been implicated in many acute human diseases through induction of ferroptosis [96,97]. Hence, for SLC7A11 the direction of the impact of the drugs on its expression is consistent with other prior evidence.…”

Section: Resultssupporting

confidence: 72%

“…The CAR canonical identifiers (CAid) or Genomic Location identifiers (GLid) provided are reference genome-agnostic, stable, and globally unique. The ERCC metanodes enable the retrieval and mapping of unique identifiers and other commonly used identifiers, such as dbSNP ids [96], connected through the Allele Registry and GL Registry using the Allele Registry RESTful APIs. Moreover, we have created the CFDE Linked Data Hub (LDH) [82], a graph-based database, to extract and link tissue and cell type-specific regulatory information from SCREEN [83], GTEx [52], and other CF projects, including Roadmap Epigenome [84] and EN-TEx [85].…”

Section: Resultsmentioning

confidence: 99%

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Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Clarke,

Evangelista,

Xie

et al. 2024

Preprint

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Many biomedical research projects produce large-scale datasets that may serve as resources for the research community for hypothesis generation, facilitating diverse use cases. Towards the goal of developing infrastructure to support the findability, accessibility, interoperability, and reusability (FAIR) of biomedical digital objects and maximally extracting knowledge from data, complex queries that span across data and tools from multiple resources are currently not easily possible. By utilizing existing FAIR application programming interfaces (APIs) that serve knowledge from many repositories and bioinformatics tools, different types of complex queries and workflows can be created by using these APIs together. The Playbook Workflow Builder (PWB) is a web-based platform that facilitates interactive construction of workflows by enabling users to utilize an ever-growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem. Via a user-friendly web-based user interface (UI), workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflows are provided in reports containing textual descriptions, as well as interactive and downloadable figures and tables. To demonstrate the ability of the PWB to generate meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases sieves novel targets for individual cancer patients using data from the GTEx, LINCS, Metabolomics, GlyGen, and the ExRNA Communication Consortium (ERCC) Common Fund (CF) Data Coordination Centers (DCCs). The workflows created with the PWB can be published and repurposed to tackle similar use cases using different inputs. The PWB platform is available from:https://playbook-workflow-builder.cloud/.

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Clarke,

Evangelista,

Xie

et al. 2024

Preprint

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“…In the nucleus, NRF2 heterodimerizes with an array of transcriptional regulatory proteins, such as Jun and Fos, and interacts with antioxidant response cis-elements (AREs) located within promoter regions regulating SLC7A11/xCT transcription [80]. NRF2 overexpression enhances SLC7A11/xCT levels, resulting in increased GSH biosynthesis and in the protection of cells from oxidative damage [16]. The transcription of several other antioxidant response-associated target genes, such as NADPH-generating enzyme genes, is also regulated by NRF2 [81].…”

Section: Nuclear Translocation Of Nrf2 Depends On Fpr2 Stimulationmentioning

confidence: 99%

“…Therefore, the increased expression of SLC7A11/xCT on cancer cell surfaces enhances the uptake of cystine for intracellular GSH synthesis [11,12]. SLC7A11/xCT is primarily expressed in the brain [13] and plays functional roles in the pathophysiology of cancer and other diseases such as cardiovascular [14,15] and neurodegenerative [16] disease. Glioma cancer cells release high amounts of glutamate in the brain [17,18], suggesting the activation of the xCT system and the generation of a glutamate-rich microenvironment, which has a significant impact on the proliferation and matrix invasion of these cells [19].…”

Section: Introductionmentioning

confidence: 99%

Formyl-Peptide Receptor 2 Signaling Modulates SLC7A11/xCT Expression and Activity in Tumor Cells

Pecchillo Cimmino,

Punziano,

Panico

et al. 2024

Antioxidants

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Cancer cells exhibit high levels of oxidative stress and consequently require a high amount of cysteine for glutathione synthesis. Solute Carrier Family 7 Member 11 (SLC7A11), or xCT, mediates the cellular uptake of cystine in exchange for intracellular glutamate; imported extracellular cystine is reduced to cysteine in the cytosol through a NADPH-consuming reduction reaction. SLC7A11/xCT expression is under the control of stress-inducing conditions and of several transcription factors, such as NRF2 and ATF4. Formyl-peptide receptor 2 (FPR2) belongs to the FPR family, which transduces chemotactic signals mediating either inflammatory or anti-inflammatory responses according to the nature of its ligands and/or FPR2 binding with other FPR isoforms. The repertoire of FPR2 agonists with anti-inflammatory activities comprises WKYMVm peptide and Annexin A1 (ANXA1), and the downstream effects of the intracellular signaling cascades triggered by FPR2 include NADPH oxidase (NOX)-dependent generation of reactive oxygen species. Herein, we demonstrate that stimulation of CaLu-6 cells with either WKYMVm or ANXA1: (i) induces the redox-regulated activation of SLC7A11/xCT; (ii) promotes the synthesis of glutathione; (iii) prevents lipid peroxidation; and (iv) favors NRF2 nuclear translocation and activation. In conclusion, our overall results demonstrate that FPR2 agonists and NOX modulate SLC7A11/xCT expression and activity, thereby identifying a novel regulative pathway of the cystine/glutamate antiport that represents a new potential therapeutical target for the treatment of human cancers.

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“…However, the cell membrane remains intact, the nucleus size is normal, and chromatin concentration does not change [ 4 , 5 ]. Biochemically, during peroid of ferroptosis, the synthesis of GSH and the activity of GPX4 in cells are significantly reduced, leading to reduced lipid peroxidase metabolism [ 6 ]. Genetically speaking, ferroptosis is a biological process regulated by multiple genes, mainly involving genetic changes in iron homeostasis and lipid peroxidation metabolism [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study

Liu,

Yu,

Sun

et al. 2024

Heliyon

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Ferroptosis and Neurodegenerative Diseases: Insights into the Regulatory Roles of SLC7A11

Cited by 12 publications

References 179 publications

Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Formyl-Peptide Receptor 2 Signaling Modulates SLC7A11/xCT Expression and Activity in Tumor Cells

Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study

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