scholarly journals D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Yansong Guo ◽  
Wei Li ◽  
Mingming Qian ◽  
Ting Jiang ◽  
Ping Guo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Contrast Media ◽  
Cell Viability ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Ros Production ◽  
Cell Adhesion Molecule 1

Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI.

scholarly journals Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells

2019 ◽  
Vol 20 (21) ◽  
pp. 5383 ◽  
Author(s):  
Li Zhang ◽  
Feifei Wang ◽  
Qing Zhang ◽  
Qiuming Liang ◽  
Shumei Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
Caspase 9 ◽  
Protein Levels ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Adhesion Molecule 1

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1β (IL-1β) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-β, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.

Abstract 452: Serine Carboxypeptidase 1 Mediates Vascular Remodeling by Increasing Inflammatory Cell Infiltration

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ting-Hein Lee ◽  
Joseph Miano
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Remodeling ◽  
Cell Adhesion Molecule ◽  
Inflammatory Cell ◽  
Catalytic Triad ◽  
Serine Carboxypeptidase ◽  
Cell Adhesion Molecule 1

In pathological vascular remodeling, contractile vascular smooth muscle cells (VSMCs) switch their phenotype to highly proliferative and migratory states leading to neointimal formation. Inflammatory cell recruitment and infiltration, which is dependent on the increased expression of adhesion molecules on the endothelial cells, is a key event to initiate SMC phenotypic modulation in vascular remodeling. Serine carboxypeptidase 1 (scpep1), a novel protease containing the putative catalytic triad (Ser-Asp-His) common to all members of the serine protease family, has been proved to be involved in vascular remodeling by promoting SMC proliferation and migration in a catalytic triad-dependent manner. To determine whether Scpep1 modulates leukocyte adhesion and infiltration, a flow-induced model of vascular remodeling was conducted in wild-type (WT) or Scpep1 knockout (KO) mice. Scpep1-null mice show a decreased number of infiltrated leukocytes into the intima and media compared to WT mice. Further, mice devoid of Scpep1 show a dramatic reduction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression in vessels in comparison with that of WT mice. Consistent with our in vivo data, the expression levels of ICAM-1 and VCAM-1 on human umbilical vein endothelial cells (HUVECs) transfected with SiRNA against Scpep1 were significantly decreased after TNF-α treatment. Taken together, these data suggest that Scpep1 may increase leukocyte extravasation by increasing the expression of VCAM-1 and ICAM-1 adhesion molecules.

scholarly journals Interleukin-4 (IL-4) and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common gamma chain

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4286-4295 ◽  
Author(s):  
B Schnyder ◽  
S Lugli ◽  
N Feng ◽  
H Etter ◽  
RA Lutz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Interleukin 4 ◽  
Vascular Cell Adhesion ◽  
Gamma Chain ◽  
Vascular Cell ◽  
The Common ◽  
Cell Adhesion Molecule 1

Interleukin-4 (IL-4) and IL-13 exert similar, nonadditive effects on endothelial cells, inducing vascular cell adhesion molecule-1 (VCAM-1) expression and subsequent transmigration of eosinophils. The receptor for IL-4 and IL-13 was described as a shared heteromultimeric complex in which the common gamma-chain (gamma c) subunit was essential for activity. Endothelial cell bound both cytokines with high affinity; by flow cytofluorometry and reverse transcription-polymerase chain reaction (RT-PCR), they expressed IL-4 receptor alpha (IL-4R alpha) but did not express the gamma c of the IL-2R. Radioligand cross-linking experiments followed by immunoprecipitation with the monoclonal antibody (MoAb) S697 to the IL-4R alpha showed IL-4-specific binding at 130 kD, the IL-4R alpha, and to a minor extent to a double band coimmunoprecipitated at 65 to 75 kD. [125 I]IL-13 bound predominantly to the 65- to 75- kD band and with a trace amount of binding at 130 kD. However, no ligand-cross-linked receptor was precipitated by the MoAb S697, indicating a cognate novel IL-13-binding subunit. Excess unlabeled IL-4 completely displaced IL-13 binding. Similarly, nonsignaling IL-4 (Y124D)-mutant abolished IL-4- and IL-13-mediated signal transduction. Unlabeled IL-13 competed successfully for IL-4 binding at 65 to 75 kD but was unable to completely displace Il-4 from its binding to the IL-4R alpha. The MoAb TUGh4, specific for the gamma c, failed to precipitate ligand-cross-linked IL-4R and IL-13R. Therefore, the subunit structure of the functional receptors for IL-4 and IL-13 on human endothelial cells does not use or require the common gamma c of the IL-2R.

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