Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P<0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P<0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

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The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization

BioMed Research International ◽

10.1155/2013/362918 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Hongyang Gao ◽

Yang You ◽

Guoping Zhang ◽

Feng Zhao ◽

Ziyi Sha ◽

...

Keyword(s):

Endothelial Cells ◽

Sciatic Nerve ◽

Nerve Fiber ◽

Schwann Cells ◽

Vascular Endothelial Cells ◽

Neurological Function ◽

Control Group ◽

Vascular Endothelial ◽

Fiber Reinforced ◽

3D Scaffolds

To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function.

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Protein kinase C regulates FLT1 abundance and stimulates its cleavage in vascular endothelial cells with the release of a soluble PlGF/VEGF antagonist

Experimental Cell Research ◽

10.1016/j.yexcr.2013.07.005 ◽

2013 ◽

Vol 319 (17) ◽

pp. 2578-2587 ◽

Cited By ~ 14

Author(s):

Nandita S. Raikwar ◽

Kang Z. Liu ◽

Christie P. Thomas

Keyword(s):

Endothelial Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Kinase C

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Requirement for Protein Kinase C θ for Cell Cycle Progression and Formation of Actin Stress Fibers and Filopodia in Vascular Endothelial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.272.45.28704 ◽

1997 ◽

Vol 272 (45) ◽

pp. 28704-28711 ◽

Cited By ~ 66

Author(s):

Shaoqing Tang ◽

Kathleen G. Morgan ◽

Christopher Parker ◽

J. Anthony Ware

Keyword(s):

Cell Cycle ◽

Endothelial Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Cell Cycle Progression ◽

Vascular Endothelial Cells ◽

Stress Fibers ◽

Vascular Endothelial ◽

Cycle Progression ◽

Kinase C

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Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

Cellular Physiology and Biochemistry ◽

10.1159/000487033 ◽

2018 ◽

Vol 45 (2) ◽

pp. 558-571 ◽

Cited By ~ 8

Author(s):

Yun Yi ◽

Yulin Shen ◽

Qin Wu ◽

Jingan Rao ◽

Shu Guan ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Viability ◽

Western Blotting ◽

High Glucose ◽

Vascular Endothelial Cells ◽

Control Group ◽

Vascular Endothelial ◽

A2b Receptor ◽

High Glucose Group ◽

Glucose Group

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucose-induced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A2B siRNA. The expression of the adenosine A2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

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Expression of Concern: Identification of nitric oxide as an endogenous activator of the AMP-activated protein kinase in vascular endothelial cells.

Journal of Biological Chemistry ◽

10.1074/jbc.ec119.009611 ◽

2019 ◽

Vol 294 (25) ◽

pp. 10027-10027

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Protein Kinase ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Amp Activated Protein Kinase

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Protein kinase Cε (PKCε) regulates BCL-2 expression in vascular endothelial cells (EC) and protects against apoptosis

Vascular Pharmacology ◽

10.1016/j.vph.2006.08.048 ◽

2006 ◽

Vol 45 (3) ◽

pp. 192

Author(s):

R. Steinberg ◽

O. Harari ◽

E. Lidington ◽

A. Samarel ◽

M. Ohba ◽

...

Keyword(s):

Endothelial Cells ◽

Protein Kinase ◽

Vascular Endothelial Cells ◽

Vascular Endothelial

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Ablation of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) in Vascular Endothelial Cells Enhances Insulin Sensitivity by Reducing Visceral Fat and Suppressing Angiogenesis

Molecular Endocrinology ◽

10.1210/me.2010-0412 ◽

2012 ◽

Vol 26 (1) ◽

pp. 95-109 ◽

Cited By ~ 7

Author(s):

Kazuhito Tawaramoto ◽

Ko Kotani ◽

Mitsuru Hashiramoto ◽

Yukiko Kanda ◽

Tomoki Nagare ◽

...

Keyword(s):

Endothelial Cells ◽

Insulin Sensitivity ◽

Protein Kinase ◽

Vascular Endothelial Cells ◽

Whole Body ◽

Vascular Endothelial ◽

Dependent Protein Kinase ◽

Dependent Protein

Abstract The phosphatidylinositol 3-kinase signaling pathway in vascular endothelial cells is important for systemic angiogenesis and glucose metabolism. In this study, we addressed the precise role of the 3-phosphoinositide-dependent protein kinase 1 (PDK1)-regulated signaling network in endothelial cells in vivo, using vascular endothelial PDK1 knockout (VEPDK1KO) mice. Surprisingly, VEPDK1KO mice manifested enhanced glucose tolerance and whole-body insulin sensitivity due to suppression of their hepatic glucose production with no change in either peripheral glucose disposal or even impaired vascular endothelial function at 6 months of age. When mice were fed a standard diet at 6 months of age and a high-fat diet at 3 months of age, hypertrophy of epididymal adipose tissues was inhibited, adiponectin mRNA was significantly increased, and mRNA of MCP1, leptin, and TNFα was decreased in the white adipose tissue of VEPDK1KO mice in comparison with controls. Consequently, both the circulating adiponectin levels and the activity of hepatic AMP-activated protein kinase were significantly increased, subsequently enhancing whole-body insulin sensitivity and energy expenditure with increased hepatic fatty acid oxidation in VEPDK1KO mice. These results provide the first in vivo evidence that lowered angiogenesis through the deletion of PDK1 signaling not only interferes with the growth of adipose tissue but also induces increased energy expenditure due to amelioration of the adipocytokine profile. This demonstrates an unexpected role of PDK1 signaling in endothelial cells on the maintenance of proper glucose homeostasis through the regulation of adipocyte development.

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