ArticleThe Biochemical journal2002
Implication of the small GTPase Rac1 in the generation of reactive oxygen species in response to beta-amyloid in C6 astroglioma cells.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Rho Signaling in Synaptic Plasticity, Memory, and Brain Disorders.Frontiers in cell and developmental biology · 2021Review
- Paeoniflorin ameliorates Aβ-stimulated neuroinflammation via regulation of NF-κB signaling pathway and Aβ degradation in C6 glial cells.Nutrition research and practice · 2020Article
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Amyloid beta: structure, biology and structure-based therapeutic development.Acta pharmacologica Sinica · 2017Review
- The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain.Molecular neurobiology · 2016Review
- NADPH oxidase-2: linking glucose, acidosis, and excitotoxicity in stroke.Antioxidants & redox signaling · 2015Article
- Protein prenylation and synaptic plasticity: implications for Alzheimer's disease.Molecular neurobiology · 2014Review
- β-Amyloid-evoked apoptotic cell death is mediated through MKK6-p66shc pathway.Neuromolecular medicine · 2014Article
- Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer disease.The Journal of biological chemistry · 2013Article
- Isoprenoids, small GTPases and Alzheimer's disease.Biochimica et biophysica acta · 2010Review
- Article
- Regulation of the brain isoprenoids farnesyl- and geranylgeranylpyrophosphate is altered in male Alzheimer patients.Neurobiology of disease · 2009Article
- Rac1 modulates stimulus-evoked Ca(2+) release in neuronal growth cones via parallel effects on microtubule/endoplasmic reticulum dynamics and reactive oxygen species production.Molecular biology of the cell · 2009Article
- An in vitro screening cascade to identify neuroprotective antioxidants in ALS.Free radical biology & medicine · 2009Article
- Advances on the understanding of the origins of synaptic pathology in AD.Current genomics · 2007Article
- Essential role of STAT1 in caspase-independent cell death of activated macrophages through the p38 mitogen-activated protein kinase/STAT1/reactive oxygen species pathway.Molecular and cellular biology · 2005Article
- Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2-chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes.British journal of pharmacology · 2004Article
- Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins.Journal of cellular and molecular medicineReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exogenous application of beta-amyloid (Abeta(25-35), a fragment of Abeta(1-42)) significantly elevated levels of reactive oxygen species (ROS) in C6 astroglioma cells, as measured by confocal microscopic analysis of H(2)O(2)-sensitive 2',7'-dichlorofluorescin fluorescence. Subsequent characterization of the signalling pathway revealed that expression of RacN17, a dominant-negative Rac1 mutant, completely blocked Abeta(25-35)-induced generation of ROS, which is indicative of the crucial role played by Rac GTPase in this process. To better understand the downstream mediators affected by Rac, we assessed the degree to which inhibition of cytosolic phospholipase A(2) (cPLA(2)) and 5-lipoxygenase (5-LO) contributed to the response and found that inhibition of either enzyme completely blocked Abeta(25-35)-induced ROS generation, indicating its dependence on arachidonic acid synthesis and metabolism to leukotrienes (e.g. leukotriene B(4)). Consistent with those findings, Abeta(25-35) Rac-dependently stimulated translocation of 5-LO to the nuclear envelope and increased intracellular levels of leukotriene B(4), while exogenous application of leukotriene B(4) increased intracellular H(2)O(2) via BLT, its cell-surface receptor. In addition to the aforementioned downstream mediators, inhibition of phosphoinositide 3-kinase (PI 3-kinase), an enzyme situated upstream of Rac, also completely blocked Abeta(25-35)-induced H(2)O(2) generation. Our findings thus demonstrate that PI 3-kinase, Rac, cPLA(2) and 5-LO are all essential components of the beta-amyloid signaling cascade leading to generation of ROS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.