ArticleOxidative medicine and cellular longevity2015
hCLOCK Causes Rho-Kinase-Mediated Endothelial Dysfunction and NF-κB-Mediated Inflammatory Responses.
Article in Oxidative medicine and cellular longevity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Circadian rhythm and the molecular clock in endothelial function of the cardiovascular system.Molecular and cellular biochemistry · 2026Review
- Rho-GTPases subfamily: cellular defectors orchestrating viral infection.Cellular & molecular biology letters · 2025Review
- ZNF143 inhibits hepatocyte mitophagy and promotes non-alcoholic fatty liver disease by targeting increased lncRNA NEAT1 expression to activate ROCK2 pathway.Epigenetics · 2023Article
- Combination of nicotinamide mononucleotide and troxerutin induces full protection against doxorubicin-induced cardiotoxicity by modulating mitochondrial biogenesis and inflammatory response.Molecular biology reports · 2022Article
- Mechanical Stretch Promotes Macrophage Polarization and Inflammation via the RhoA-ROCK/NF-BioMed research international · 2022Article
- A wrinkle in time: circadian biology in pulmonary vascular health and disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Protective effects of SS-31 against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression.American journal of translational research · 2020Article
- Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F‑actin pathways.International journal of oncology · 2018Article
- Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF‑α.Molecular medicine reports · 2018Article
- BMAL1 suppresses ROS-induced endothelial-to-mesenchymal transition and atherosclerosis plaque progression via BMP signaling.American journal of translational research · 2018Article
- Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance.Oxidative medicine and cellular longevity · 2018Review
- A Positive Feedback Loop of Profilin-1 and RhoA/ROCK1 Promotes Endothelial Dysfunction and Oxidative Stress.Oxidative medicine and cellular longevity · 2018Article
- CLOCK Promotes Endothelial Damage by Inducing Autophagy through Reactive Oxygen Species.Oxidative medicine and cellular longevity · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe human Circadian Locomotor Output Cycle protein Kaput (CLOCK) gene was originally discovered as a regulator of essential human daily rhythms. This seemingly innocuous gene was then found to be associated with a multitude of human malignancies, via several biochemical pathways. We aimed to further investigate the role of hCLOCK in the hypoxia-oxidative stress response system at the biochemical level.
methodsExpression levels of Rho GTPases were measured in normoxic and hypoxic states. The effect of hCLOCK on the hypoxic response was evaluated with the use of a retroviral shRNA vector system, a Rho inhibitor, and a ROS scavenger by analyzing expression levels of hCLOCK, Rho GTPases, and NF-κB pathway effectors. Finally, in vitro ROS production and tube formation in HUVECs were assessed.
resultsHypoxia induces ROS production via hCLOCK. hCLOCK activates the RhoA and NF-κB signaling pathways. Conversely, inhibition of hCLOCK deactivates these pathways. Furthermore, inhibition of RhoA or decreased levels of ROS attenuate these pathways, but inhibition of RhoA does not lead to decreased levels of ROS. Overall findings show that hypoxia increases the expression of hCLOCK, which leads to ROS production, which then activates the RhoA and NF-κB pathways.
conclusionOur findings suggest that hypoxic states induce vascular oxidative damage and inflammation via hCLOCK-mediated production of ROS, with subsequent activation of the RhoA and NF-κB pathways.
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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.