Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGFβ/NADPH Oxidases/ROS Signaling Pathway.
Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGFβ/NADPH Oxidases/ROS Signaling Pathway.
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6-磷酸脱氢酶缺乏症激活通过TGFβ/NADPH氧化酶/ROS信号通路介导的内皮细胞和白细胞粘附。
DOI：
10.3390/ijms21207474
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发表时间：
2020-10-10
影响因子：
5.6
通讯作者：
Jain SK
中科院分区：
文献类型：
--
作者：
Parsanathan R;Jain SK
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic inherited trait among humans, affects ~7% of the global population, and is associated with excess risk of cardiovascular disease (CVD). Transforming growth factor-β (TGF-β) regulates immune function, proliferation, epithelial-mesenchymal transition, fibrosis, cancer, and vascular dysfunction. This study examined whether G6PD deficiencies can alter TGF-β-mediated NADPH oxidases (NOX) and cell adhesion molecules (CAM) in human aortic endothelial cells (HAEC). Results show that treatment with high glucose and the saturated free fatty acid palmitate significantly downregulated G6PD; in contrast, mRNA levels of TGF-β components, NOX and its activity, and reactive oxygen species (ROS) were significantly upregulated in HAEC. The expression levels of TGF-β and its receptors, NOX and its activity, and ROS were significantly higher in HG-exposed G6PD-deficient cells (G6PD siRNA) compared to G6PD-normal cells. The protein levels of adhesion molecules (ICAM-1 and VCAM-1) and inflammatory cytokines (MCP-1 and TNF) were significantly increased in HG-exposed G6PD-deficient cells compared to G6PD-normal cells. The adherence of monocytes (SC cells) to HAEC was significantly elevated in HG-treated G6PD-deficient cells compared to control cells. Pharmacological inhibition of G6PD enhances ROS, NOX and its activity, and endothelial monocyte adhesion; these effects were impeded by NOX inhibitors. The inhibition of TGF-β prevents NOX2 and NOX4 mRNA expression and activity, ROS, and adhesion of monocytes to HAEC. L-Cysteine ethyl ester (cell-permeable) suppresses the mRNA levels of TGF-β and its receptors, along with NOX2 and NOX4, and decreases NOX activity, ROS, and adhesion of monocytes to HAEC. This suggests that G6PD deficiency promotes TGF-β/NADPH oxidases/ROS signaling, the expression of ICAM-1 and VCAM-1, and the adhesion of leukocytes to the endothelial monolayer, which can contribute to a higher risk for CVD.
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TGF-β和活性氧的相互调节：纤维化的不良周期。
影响因子：
11.4
作者：
Liu RM;Desai LP
通讯作者：
Desai LP
DOI：
10.1161/atvbaha.116.307308
发表时间：
2016-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Delaney MK;Kim K;Estevez B;Xu Z;Stojanovic-Terpo A;Shen B;Ushio-Fukai M;Cho J;Du X
通讯作者：
Du X
影响因子：
5
作者：
Montorfano, Ignacio;Becerra, Alvaro;Simon, Felipe
通讯作者：
Simon, Felipe
DOI：
10.1165/rcmb.2013-0519oc
发表时间：
2015-01-01
影响因子：
6.4
作者：
Jaffer, Omar A.;Carter, A. Brent;Anderson, Mark E.
通讯作者：
Anderson, Mark E.
影响因子：
1.2
作者：
Murray, Clinton K.;Chinevere, Troy D.;Hospenthal, Duane R.
通讯作者：
Hospenthal, Duane R.