A novel antioxidant peptide derived from wheat germ prevents high glucose-induced oxidative stress in vascular smooth muscle cells in vitro

2017 ◽  
Vol 8 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Siyuan Chen ◽  
Dingbo Lin ◽  
Yulong Gao ◽  
Xiaozhou Cao ◽  
Xinchun Shen
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Molecular Mechanism ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Wheat Germ ◽  
Ros Generation

A possible molecular mechanism of AOP in the inhibition of high glucose-induced ROS generation in VSMCs.

Wheat germ-derived peptide ADWGGPLPH abolishes high glucose-induced oxidative stress via modulation of the PKCζ/AMPK/NOX4 pathway

2020 ◽  
Vol 11 (8) ◽  
pp. 6843-6854 ◽  
Author(s):  
Fang Wang ◽  
Zebin Weng ◽  
Yi Lyu ◽  
Yifan Bao ◽  
Juncheng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Wheat Germ ◽  
Muscle Cells ◽  
Antioxidative Effect ◽  
Underlying Mechanisms

This study explores the antioxidative effect of a specific wheat germ-derived peptide on high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs) and the underlying mechanisms.

scholarly journals Geranylgeranyl Transferase-I Knockout Inhibits Oxidative Injury of Vascular Smooth Muscle Cells and Attenuates Diabetes-Accelerated Atherosclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Guo-Ping Chen ◽  
Jian Yang ◽  
Guo-Feng Qian ◽  
Wei-Wei Xu ◽  
Xiao-Qin Zhang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Oxidative Injury ◽  
Accelerated Atherosclerosis ◽  
Vsmc Proliferation ◽  
Geranylgeranyl Transferase

The proliferation of vascular smooth muscle cells (VSMCs) induced by oxidative injury is one of the main features in diabetes-accelerated atherosclerosis. Geranylgeranyl transferase-I (GGTase-I) is an essential enzyme mediating posttranslational modification, especially the geranylgeranylation of small GTPase, Rac1. Our previous studies found that GGTase-I played an important role in diabetes-accelerated atherosclerosis. However, its exact role is largely unclear. In this study, mouse conditional knockout of VSMC GGTase-I (Pggt1bΔ/Δ mice) was generated using the CRISPR/Cas9 system. The mouse model of diabetes-accelerated atherosclerosis was induced by streptozotocin injections and an atherogenic diet. We found that GGTase-I knockout attenuated diabetes-accelerated atherosclerosis in vivo and suppressed high-glucose-induced VSMC proliferation in vitro. Moreover, after a 16-week duration of diabetes, Pggt1bΔ/Δ mice exhibited lower α-smooth muscle actin (α-SMA) and nitrotyrosine level, Rac1 activity, p47phox and NOXO1 expression, and phospho-ERK1/2 and phosphor-JNK content than wild-type mice. Meanwhile, the same changes were found in Pggt1bΔ/Δ VSMCs cultured with high glucose (22.2 mM) in vitro. In conclusion, GGTase-I knockout efficiently blocked diabetes-accelerated atherosclerosis, and this protective effect must be related to the inhibition of VSMC proliferation. The potential mechanisms probably involved interfering Rac1 geranylgeranylation, inhibiting the assembly of NADPH oxidase cytosolic regulatory subunits, reducing oxidative injury, and decreasing ERK1/2 and JNK phosphorylation.

scholarly journals Yixintongmai Inhibits Proliferation, Migration and Promotes Apoptosis of Vascular Smooth Muscle Cells Cultured with High Glucose

2020 ◽  
Author(s):  
JingJing Guo ◽  
Di Zhao ◽  
Pingshuan Dong
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Cell Counting ◽  
Ros Generation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Abstract Background: This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. Methods: VSMCs of the thoracic aorta from 5–8 weeks male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The effects of yixintongmai on proliferation, migration, and apoptosis of VSMCs cultured with high glucose were evaluated. The concentration of yixintongmai powder at 360 μg/ml was chosen for this study according to pre-experimental results. Results: Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P<0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P<0.001) and the expression of PCNA (0.74 ± 0.08 folds, P<0.001) as compared with high glucose. Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P<0.001; scratch wound assay: 2.69 ± 0.22 folds, P<0.001) and the expression of MMP-9 (0.87 ± 0.03 folds, P<0.001) as compared with high glucose. Yixintongmai promoted the apoptosis of VSMCs (0.36 ± 0.12 folds, P<0.001) and inhibited the expression of bcl-2 (0.83 ± 0.07 folds, P<0.01) as compared with high glucose. Yixintongmai inhibited ROS generation (0.58 ± 0.01 folds, P<0.001) and the expression of NF-κB (0.71 ± 0.07 folds, P<0.001) of VSMCs as compared with high glucose. Conclusions: Yixintongmai inhibits the proliferation, migration and promotes the apoptosis of VSMCs cultured with high glucose, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.

Abstract 462: Ascl3 Protects Vascular Smooth Muscle Cells Against Oxidative Stress

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Swarajit K Biswas ◽  
Liliana Hernandez ◽  
Yan Xiao ◽  
Mushtaq Ahmad ◽  
Minerva T Garcia-Barrio
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mitochondrial Pathway ◽  
Protective Role ◽  
Over Expression

Atherosclerosis initiation and progression depends on multiple risk factors and is sustained by self-perpetuating inflammatory cellular and molecular events that ultimately translate into increased oxidative stress inducing endothelial dysfunction, macrophage activation and altering vascular smooth muscle cell (VSMC) homeostasis. Our initial work identified the under-characterized bHLH achaete-scute like 3, ASCL3, as a pro-proliferative anti-apoptotic factor in VSMC and prompted the hypothesis that ASCL3 plays a protective role against oxidative stress in VSMC. We determined that ASCL3 expression is up-regulated in the media and lesions of the atherosclerotic aorta in ApoE-mice fed a high fat diet. In vitro , ASCL3 expression is consistent with an adaptive role in oxidative stress. In primary RASMC, time- and dose-response to H 2 O 2 (0.5-2mM, 4-24h) result in marked ASCL3 mRNA increase (~10-fold) at low concentrations or shorter times and is reduced as oxidative stress increases. siRNA knockdown of ASCL3 increases susceptibility of RASMC to 0.25mM H 2 O 2 (low dose) as determined by caspase-3 activation. Stable over-expression of ASCL3 in A7r5 cells results in enhanced protection at higher doses of H 2 O 2 , and is associated with higher AKT and ERK1/2 phosporylation. This protective effect involves the mitochondrial pathway since ASCL3 up-regulates Bcl-2/Bax ratio in basal and induced conditions (0.4mM, 4h), inhibits mitochondrial depolarization, prevents mitochondrial fragmentation and preserves mitochondrial DNA. ROS levels are significantly reduced in ASCL3 over-expressing cells (0.2mM, 2h). ASCL3 over-expression appears to increase mitochondrial density and results in altered mitochondrial and cristae morphology as determined by TEM. Surprisingly, subcellular localization studies indicate that ASCL3 localizes primarily to the mitochondria. In summary, low oxidative stress in VSMC promotes survival, with enhanced proliferation, and as it increases, induces adaptation associated with an antioxidant gene expression profile. Eventually high oxidative stress leads to cell death. Altogether, our data indicate that ASCL3 plays a protective role in the survival and adaptation of vascular smooth muscle cells to oxidative stress.

Role of oxidative stress in high glucose-induced decreased expression of Giα proteins and adenylyl cyclase signaling in vascular smooth muscle cells

2008 ◽  
Vol 294 (6) ◽  
pp. H2845-H2854 ◽  
Author(s):  
Yuan Li ◽  
Magda Descorbeth ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Diabetic Rats ◽  
Adenylyl Cyclase Activity

We have recently shown that aorta from streptozotocin (STZ)-induced diabetic rats and A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited decreased levels of inhibitory guanine nucleotide regulatory protein (Gi)α proteins. In the present studies, we investigated the implication of oxidative stress in the hyperglycemia/diabetes-induced decreased expression of the Giα protein and adenylyl cyclase signaling in VSMCs by using antioxidants. The levels of Giα proteins were significantly decreased in A10 VSMCs exposed to high glucose and in aortic VSMCs from STZ-diabetic rats compared with control cells and were restored to control levels by antioxidants. In addition, 111Mn-tetralis(benzoic acid porphyrin) and uric acid, scavengers of peroxynitrite, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase but not catalase, also restored the high glucose-induced decreased expression of Giα proteins to the control levels in A10 VSMCs. Furthermore, the enhanced production of superoxide anion (O2−) and increased activity of NADPH oxidase in these cells were also restored to control levels by diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, the diminished inhibition of adenylyl cyclase activity by inhibitory hormones and forskolin-stimulated adenylyl cyclase activity by low concentrations of GTPγS as well as the enhanced stimulation of adenylyl cyclase by stimulatory agonists in hyperglycemic cells were restored to control levels by antioxidant treatments. These results suggest that high glucose-induced decreased levels of Giα proteins and associated signaling in A10 VSMCs may be attributed to the enhanced oxidative stress due to augmented levels of peroxynitrite and not to H2O2.

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