The RhoA/ROCK-I/MLC pathway is involved in the ethanol-induced apoptosis by anoikis in astrocytes
Open accessAbstract
Anoikis is a programmed cell death induced by loss of anchorage that is involved in tissue homeostasis and disease. Ethanol is an important teratogen that induces marked central nervous system (CNS) dysfunctions. Here we show that astrocytes exposed to ethanol undergo morphological changes associated with anoikis, including the peripheral reorganization of both focal adhesions and actin-myosin system, cell contraction, membrane blebbing and chromatin condensation. We found that either the small GTPase RhoA or its effector ROCK-I (Rho kinase), promotes membrane blebbing in astrocytes. Ethanol induces a ROCK-I activation that is mediated by RhoA, rather than by caspase-3 cleavage. Accordingly, the RhoA inhibitor C3, completely abolishes the ethanol-induced ROCK-I activation. Furthermore, inhibition of both RhoA and ROCK prevents the membrane blebbing induced by ethanol. Ethanol also promotes myosin light chain (MLC) phosphorylation, which might be involved in the actin-myosin contraction. All of these findings strongly support that ethanol-exposed astrocytes undergo apoptosis by anoikis and also that the RhoA/ROCK-I/MLC pathway participates in this process.
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RhoA signalling might potentially contribute to cell death, because it can promote apoptosis in low-adhesion environments by increasing cell contractility.
“RhoA signalling might also potentially contribute to cell death, because it can promote apoptosis in low-adhesion environments by increasing cell contractility, explaining why ROCK inhibitors are a standard component of media for stem cells and organoid isolation and maintenance in culture 77-81 .”
From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [80]
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Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain
Alfonso-Loeches, S., & Guerri, C. (2011) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2011.580567 · Cited by 254 · see citing works
Self-citationMeiring, J. C. M., Mahapatra, V., Liu, R., Gravett, M. S. C., Morren, D., Saunders, H. A. J., Choi, S. R., Pelster José, A., Karhanova, A., Metallidou, I., et al. (2026) · Nature Cell Biology · doi:10.1038/s41556-026-02079-4
- Authors
- Miñambres, R., Guasch, R. M., Perez-Aragó, A., & Guerri, C.
- Affiliations
- Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, c/EP Autopista del Saler 16-3, 46013-Valencia, Spain
- Centro de Investigacion Principe Felipe (ES)
- ORCID
- Guerri, Consuelo
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2006-01-15
- Volume
- 119
- Issue
- 2
- Pages
- 271-282
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1996989584
- Cited by
- 94
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 8 · 2012: 6
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Generalitat Valenciana
- Instituto de Salud Carlos III (G03/005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- anoikis, ethanol-induced apoptosis, astrocytes, RhoA, ROCK1, myosin light chain phosphorylation, membrane blebbing, focal adhesions, caspase-3, C3 inhibitor, teratogenicity, central nervous system disorders
- MeSH terms
- Actins, Ethanol, Animals, Astrocytes, Cells, Cultured, Enzyme Activation, Myosins, Protein Serine-Threonine Kinases, Myosin Light Chains, Caspases, rhoA GTP-Binding Protein, Anoikis, Intracellular Signaling Peptides and Proteins, Cell Shape, Rats, Caspase 3, rho-Associated Kinases
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