ArticlePloS one2014
Complex regulation of PKCβ2 and PDK-1/AKT by ROCK2 in diabetic heart.
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 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Cranberry improves metabolic syndrome-related organ dysfunction in rats by modulating AMPK/SREBP1, ROCK1 and TGF-β1.Scientific reports · 2025Article
- Identification of key genes of diabetic cardiomyopathy in hiPSCs-CMs based on bioinformatics analysis.Molecular and cellular biochemistry · 2024Article
- Rho-kinase ROCK inhibitors reduce oligomeric tau protein.Neurobiology of aging · 2020Article
- MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells.Open life sciences · 2020Article
- A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells.PloS one · 2018Article
- 3-Phosphoinositide Dependent Protein Kinase-1 (PDK-1) Promotes Migration and Invasion in Gastric Cancer Cells Through Activating the NF-κB Pathway.Oncology research · 2017Article
- The Rho kinase inhibitor, fasudil, ameliorates diabetes-induced cardiac dysfunction by improving calcium clearance and actin remodeling.Journal of molecular medicine (Berlin, Germany) · 2017Article
- RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels.BMC cardiovascular disorders · 2016Article
- Chronic Rho-kinase inhibition improves left ventricular contractile dysfunction in early type-1 diabetes by increasing myosin cross-bridge extension.Cardiovascular diabetology · 2015Article
- Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy.World journal of diabetes · 2015Review
- Inhibitory activities of selected Kampo formulations on human aldose reductase.BMC complementary and alternative medicine · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe RhoA/ROCK pathway contributes to diabetic cardiomyopathy in part by promoting the sustained activation of PKCβ2 but the details of their interaction are unclear. The purpose of this study was to investigate if over-activation of ROCK in the diabetic heart leads to direct phosphorylation and activation of PKCβ2, and to determine if their interaction affects PDK-1/Akt signaling.
methodsRegulation by ROCK of PKCβ2 and related kinases was investigated by Western blotting and co-immunoprecipitation in whole hearts and isolated cardiomyocytes from 12 to 14-week diabetic rats. Direct ROCK2 phosphorylation of PKCβ2 was examined in vitro. siRNA silencing was used to confirm role of ROCK2 in PKCβ2 phosphorylation in vascular smooth muscle cells cultured in high glucose. Furthermore, the effect of ROCK inhibition on GLUT4 translocation was determined in isolated cardiomyocytes by confocal microscopy.
resultsExpression of ROCK2 and expression and phosphorylation of PKCβ2 were increased in diabetic hearts. A physical interaction between the two kinases was demonstrated by reciprocal immunoprecipitation, while ROCK2 directly phosphorylated PKCβ2 at T641 in vitro. ROCK2 siRNA in vascular smooth muscle cells or inhibition of ROCK in diabetic hearts reduced PKCβ2 T641 phosphorylation, and this was associated with attenuation of PKCβ2 activity. PKCβ2 also formed a complex with PDK-1 and its target AKT, and ROCK inhibition resulted in upregulation of the phosphorylation of PDK-1 and AKT, and increased translocation of glucose transporter 4 (GLUT4) to the plasma membrane in diabetic hearts.
conclusionThis study demonstrates that over-activation of ROCK2 contributes to diabetic cardiomyopathy by multiple mechanisms, including direct phosphorylation and activation of PKCβ2 and interference with the PDK-1-mediated phosphorylation and activation of AKT and translocation of GLUT4. This suggests that ROCK2 is a critical node in the development of diabetic cardiomyopathy and may be an effective target to improve cardiac function in diabetes.
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