ArticleInternational journal of molecular sciences2020
Y-27632 Induces Neurite Outgrowth by Activating the NOX1-Mediated AKT and PAK1 Phosphorylation Cascades in PC12 Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nox1/PAK1 is required for angiotensin II-induced vascular inflammation and abdominal aortic aneurysm formation.Redox biology · 2025Article
- Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A.Stroke and vascular neurology · 2023Article
- Enumeration and Characterization of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.International journal of molecular sciences · 2023Article
- P-21 Activated Kinases in Liver Disorders.Cancers · 2023Review
- Novel Dual AChE and ROCK2 Inhibitor Induces Neurogenesis via PTEN/AKT Pathway in Alzheimer's Disease Model.International journal of molecular sciences · 2022Article
- Activation of RhoC by regulatory ubiquitination is mediated by LNX1 and suppressed by LIS1.Scientific reports · 2022Article
- Förster resonance energy transfer efficiency of the vinculin tension sensor in cultured primary cortical neuronal growth cones.Neurophotonics · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Y-27632 is known as a selective Rho-associated coiled coil-forming kinase (ROCK) inhibitor. Y-27632 has been shown to induce neurite outgrowth in several neuronal cells. However, the precise molecular mechanisms linking neurite outgrowth to Y-27632 are not completely understood. In this study, we examined the ability of Y-27632 to induce neurite outgrowth in PC12 cells and evaluated the signaling cascade. The effect of Y-27632 on the neurite outgrowth was inhibited by reactive oxygen species (ROS) scavengers such as N-acetyl cysteine (NAC) and trolox. Furthermore, Y-27632-induced neurite outgrowth was not triggered by NADPH oxidase 1 (NOX1) knockdown or diphenyleneiodonium (DPI), a NOX inhibitor. Suppression of the Rho-family GTPase Rac1, which is under the negative control of ROCK, with expression of the dominant negative Rac1 mutant (Rac1N17) prevented Y-27632-induced neurite outgrowth. Moreover, the Rac1 inhibitor NSC23766 prevented Y-27632-induced AKT and p21-activated kinase 1 (PAK1) activation. AKT inhibition with MK2206 suppressed Y-27632-induced PAK1 phosphorylation and neurite outgrowth. In conclusion, our results suggest that Rac1/NOX1-dependent ROS generation and subsequent activation of the AKT/PAK1 cascade contribute to Y-27632-induced neurite outgrowth in PC12 cells.
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