ArticleJournal of neurochemistry2005
Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial apoptotic cascade in cerebellar granule neurons.
Article in Journal of neurochemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
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Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Clostridioides difficile toxin B alone and with pro-inflammatory cytokines induces apoptosis in enteric glial cells by activating three different signalling pathways mediated by caspases, calpains and cathepsin B.Cellular and molecular life sciences : CMLS · 2022Article
- Dysregulation of Rac or Rho elicits death of motor neurons and activation of these GTPases is altered in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis.Neurobiology of disease · 2020Article
- Review
- Neuronal apoptosis induced by selective inhibition of Rac GTPase versus global suppression of Rho family GTPases is mediated by alterations in distinct mitogen-activated protein kinase signaling cascades.The Journal of biological chemistry · 2015Article
- Alterations in molecular pathways in the retina of early experimental glaucoma eyes.International journal of physiology, pathophysiology and pharmacology · 2015Article
- The potential role of rho GTPases in Alzheimer's disease pathogenesis.Molecular neurobiology · 2014Review
- Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.Frontiers in cellular neuroscience · 2014Review
- C-terminal binding proteins are essential pro-survival factors that undergo caspase-dependent downregulation during neuronal apoptosis.Molecular and cellular neurosciences · 2013Article
- Article
- The enteropathogenic Escherichia coli effector NleH inhibits apoptosis induced by Clostridium difficile toxin B.Microbiology (Reading, England) · 2010Article
- Rac1 regulates neuronal polarization through the WAVE complex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Critical involvement of Rho GTPase activity in the efficient transplantation of neural stem cells into the injured spinal cord.Molecular brain · 2009Article
- Brain extracellular matrix in neurodegeneration.Brain pathology (Zurich, Switzerland) · 2009Review
- Caspases indirectly regulate cleavage of the mitochondrial fusion GTPase OPA1 in neurons undergoing apoptosis.Brain research · 2009Article
- Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly.Developmental biology · 2009Article
- Human butyrate-induced transcript 1 interacts with hepatitis C virus NS5A and regulates viral replication.Journal of virology · 2008Article
- Brain-derived neurotrophic factor promotes long-term potentiation-related cytoskeletal changes in adult hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and toxin B from variant Clostridium difficile strain 1470.Infection and immunity · 2007Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Rho GTPases are key transducers of integrin/extracellular matrix and growth factor signaling. Although integrin-mediated adhesion and trophic support suppress neuronal apoptosis, the role of Rho GTPases in neuronal survival is unclear. Here, we have identified Rac as a critical pro-survival GTPase in cerebellar granule neurons (CGNs) and elucidated a death pathway triggered by its inactivation. GTP-loading of Rac1 was maintained in CGNs by integrin-mediated (RGD-dependent) cell attachment and trophic support. Clostridium difficile toxin B (ToxB), a specific Rho family inhibitor, induced a selective caspase-mediated degradation of Rac1 without affecting RhoA or Cdc42 protein levels. Both ToxB and dominant-negative N17Rac1 elicited CGN apoptosis, characterized by cytochrome c release and activation of caspase-9 and -3, whereas dominant-negative N19RhoA or N17Cdc42 did not cause significant cell death. ToxB stimulated mitochondrial translocation and conformational activation of Bax, c-Jun activation, and induction of the BH3-only protein Bim. Similarly, c-Jun activation and Bim induction were observed with N17Rac1. A c-jun N-terminal protein kinase (JNK)/p38 inhibitor, SB203580, and a JNK-specific inhibitor, SP600125, significantly decreased ToxB-induced Bim expression and blunted each subsequent step of the apoptotic cascade. These results indicate that Rac acts downstream of integrins and growth factors to promote neuronal survival by repressing c-Jun/Bim-mediated mitochondrial apoptosis.
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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.