ArticlePloS one2014
ROCK1 deficiency enhances protective effects of antioxidants against apoptosis and cell detachment.
Article in PloS one, 2014. 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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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Thioredoxin-Binding protein 2 and apoptosis Signal-Regulating kinase 1: redox stress sensors and therapeutic targets in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Blast-Overpressure Induced Modulation of PARP-SIRT-NRF2 Axis in Stress Signaling of Astrocytes and Microglia.Immunity, inflammation and disease · 2025Article
- Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats.Journal of ovarian research · 2024Article
- ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.FASEB bioAdvances · 2024Article
- Rho Kinases in Embryonic Development and Stem Cell Research.Archivum immunologiae et therapiae experimentalis · 2022Review
- The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease.Antioxidants (Basel, Switzerland) · 2021Review
- High-expression of ROCK1 modulates the apoptosis of lens epithelial cells in age-related cataracts by targeting p53 gene.Molecular medicine (Cambridge, Mass.) · 2020Article
- ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Rho-associated coiled-coil kinase 1 activation mediates amyloid precursor protein site-specific Ser655 phosphorylation and triggers amyloid pathology.Aging cell · 2019Article
- Cholix toxin, an eukaryotic elongation factor 2 ADP-ribosyltransferase, interacts with Prohibitins and induces apoptosis with mitochondrial dysfunction in human hepatocytes.Cellular microbiology · 2019Article
- The level of ROCK1 and ROCK2 in patients with pulmonary hypertension in plateau area.Scientific reports · 2018Article
- Disruption of ROCK1 gene restores autophagic flux and mitigates doxorubicin-induced cardiotoxicity.Oncotarget · 2018Article
- ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium.Translational vision science & technology · 2016Article
- Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro.Acta pharmacologica Sinica · 2016Article
- Novel Insights into the Roles of Rho Kinase in Cancer.Archivum immunologiae et therapiae experimentalis · 2016Review
- The kinase inhibitor D11 induces caspase-mediated cell death in cancer cells resistant to chemotherapeutic treatment.Journal of experimental & clinical cancer research : CR · 2015Article
- Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin.Cell death & disease · 2015Article
- Rho-Associated Kinase Inhibitor (Y-27632) Attenuates Doxorubicin-Induced Apoptosis of Human Cardiac Stem Cells.PloS one · 2015Article
- Dissecting the Mechanisms of Doxorubicin and Oxidative Stress-Induced Cytotoxicity: The Involvement of Actin Cytoskeleton and ROCK1.PloS one · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We have recently reported that the homologous Rho kinases, ROCK1 and ROCK2, play different roles in regulating stress-induced stress fiber disassembly and cell detachment, and the ROCK1 deficiency in mouse embryonic fibroblasts (MEF) has remarkable anti-apoptotic, anti-detachment and pro-survival effects against doxorubicin, a chemotherapeutic drug. This study investigated the roles of ROCK isoforms in doxorubicin-induced reactive oxygen species (ROS) generation which is believed to be the major mechanism underlying its cytotoxicity to normal cells, and especially to cardiomyocytes. Different antioxidants have been shown to provide a protective role reported in numerous experimental studies, but clinical trials of antioxidant therapy showed insufficient benefit against the cardiac side effect. We found that both ROCK1-/- and ROCK2-/- MEFs exhibited reduced ROS production in response to doxorubicin treatment. Interestingly, only ROCK1 deficiency, but not ROCK2 deficiency, significantly enhanced the protective effects of antioxidants against doxorubicin-induced cytotoxicity. First, ROCK1 deficiency and N-acetylcysteine (an anti-oxidant) treatment synergistically reduced ROS levels, caspase activation and cell detachment. In addition, the reduction of ROS generation in ROCK1-/- MEFs in response to doxorubicin treatment was in part through inhibiting NADPH oxidase activity. Furthermore, ROCK1 deficiency enhanced the inhibitory effects of diphenyleneiodonium (an inhibitor of NADPH oxidase) on ROS generation and caspase 3 activation induced by doxorubicin. Finally, ROCK1 deficiency had greater protective effects than antioxidant treatment, especially on reducing actin cytoskeleton remodeling. ROCK1 deficiency not only reduced actomyosin contraction but also preserved central stress fiber stability, whereas antioxidant treatment only reduced actomyosin contraction without preserving central stress fibers. These results reveal a novel strategy to enhance the protective effect of antioxidant therapy by targeting the ROCK1 pathway to stabilize the actin cytoskeleton and boost the inhibitory effects on ROS production, apoptosis and cell detachment.
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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.