Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

P-selectin is a leukocyte adhesion receptor stored in platelets and endothelial cells and is translocated to the surface upon cell activation. Purified P-selectin is oligomeric and has increased avidity for its ligand relative to the monomeric form, but whether P-selectin self-associates in the membrane of intact cells is not known. A chemical cross-linking approach was used to show that P-selectin is present as noncovalent dimers in resting platelets, human umbilical vein endothelial cells, and heterologous RIN5F cells expressing P-selectin. The results of 2-dimensional isoelectric focusing are consistent in showing P-selectin dimers as homodimers, but they are composed of a more basic subset of P-selectin than the monomers. This suggests that the dimers are a biochemically distinct subset of P-selectin. P-selectin dimers form in the endoplasmic reticulum and Golgi compartments of human umbilical vein endothelial cells only after synthesis of the mature P-selectin subunit, and are not preferentially stored in Weibel-Palade bodies as compared with the monomeric form. Platelet activation with thrombin receptor–activating peptide leads to the presence of P-selectin monomers and homodimers on the cell surface as well as P-selectin heterodimers, which are composed of P-selectin and an unidentified protein of approximately 81 kd molecular weight. In summary, these studies demonstrate that P-selectin is homodimeric in situ and that platelet activation leads to the formation of an additional activation-specific heterodimeric species. In addition, the homodimer has unique biochemical characteristics compared with the monomeric form, and dimerization occurs in the endoplasmic reticulum and Golgi compartments of endothelial cells.

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Dimerization of P-selectin in platelets and endothelial cells

Blood ◽

10.1182/blood.v96.9.3070 ◽

2000 ◽

Vol 96 (9) ◽

pp. 3070-3077 ◽

Cited By ~ 37

Author(s):

Fern J. Barkalow ◽

Kurt L. Barkalow ◽

Tanya N. Mayadas

Keyword(s):

Endothelial Cells ◽

Endoplasmic Reticulum ◽

Platelet Activation ◽

Cell Activation ◽

Leukocyte Adhesion ◽

Umbilical Vein ◽

Monomeric Form ◽

Intact Cells ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

Abstract P-selectin is a leukocyte adhesion receptor stored in platelets and endothelial cells and is translocated to the surface upon cell activation. Purified P-selectin is oligomeric and has increased avidity for its ligand relative to the monomeric form, but whether P-selectin self-associates in the membrane of intact cells is not known. A chemical cross-linking approach was used to show that P-selectin is present as noncovalent dimers in resting platelets, human umbilical vein endothelial cells, and heterologous RIN5F cells expressing P-selectin. The results of 2-dimensional isoelectric focusing are consistent in showing P-selectin dimers as homodimers, but they are composed of a more basic subset of P-selectin than the monomers. This suggests that the dimers are a biochemically distinct subset of P-selectin. P-selectin dimers form in the endoplasmic reticulum and Golgi compartments of human umbilical vein endothelial cells only after synthesis of the mature P-selectin subunit, and are not preferentially stored in Weibel-Palade bodies as compared with the monomeric form. Platelet activation with thrombin receptor–activating peptide leads to the presence of P-selectin monomers and homodimers on the cell surface as well as P-selectin heterodimers, which are composed of P-selectin and an unidentified protein of approximately 81 kd molecular weight. In summary, these studies demonstrate that P-selectin is homodimeric in situ and that platelet activation leads to the formation of an additional activation-specific heterodimeric species. In addition, the homodimer has unique biochemical characteristics compared with the monomeric form, and dimerization occurs in the endoplasmic reticulum and Golgi compartments of endothelial cells.

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Cigarette smoke extract induces prolonged endoplasmic reticulum stress and autophagic cell death in human umbilical vein endothelial cells

Cardiovascular Research ◽

10.1093/cvr/cvr165 ◽

2011 ◽

Vol 92 (1) ◽

pp. 141-148 ◽

Cited By ~ 60

Author(s):

Adam Csordas ◽

Simone Kreutmayer ◽

Christian Ploner ◽

Peter R. Braun ◽

Alexander Karlas ◽

...

Keyword(s):

Endothelial Cells ◽

Endoplasmic Reticulum ◽

Cell Death ◽

Endoplasmic Reticulum Stress ◽

Cigarette Smoke ◽

Umbilical Vein ◽

Cigarette Smoke Extract ◽

Autophagic Cell Death ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

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Evodiamine Attenuates P2X7-Mediated Inflammatory Injury of Human Umbilical Vein Endothelial Cells Exposed to High Free Fatty Acids

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/5082817 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Yun Xue ◽

Ting Guo ◽

Lifang Zou ◽

Yingxin Gong ◽

Bing Wu ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Endothelial Cells ◽

Free Fatty Acids ◽

Inflammatory Responses ◽

Umbilical Vein ◽

Human Umbilical Vein ◽

Beneficial Effects ◽

Protein Levels ◽

Umbilical Vein Endothelial Cells

Insulin resistance and type 2 diabetes mellitus (T2DM) are highly prevalent around the world. Elevated concentrations of free fatty acids (FFAs) are closely related to insulin resistance and T2DM. P2X7 receptor is an ion channel gated by ATP, which is implicated in various scenarios including immune response, pain, and inflammation. In this study, we have explored whether P2X7 receptor is involved in pathological changes in human umbilical vein endothelial cells (HUVECs) induced by high FFA treatment, and the potential beneficial effects of evodiamine. Evodiamine could effectively suppress the enhanced expression of P2X7 receptor caused by high FFAs at both mRNA and protein levels. In addition, high FFA-induced cytotoxicity, the upregulated release of ATP, and production of reactive oxygen species (ROS) could be ameliorated by evodiamine in HUVECs. Evodiamine could also reverse the decreased NO formation and the increased adhesive events of immune cells at high FFAs. Moreover, evodiamine inhibited P2X7-dependent TNF-α expression and ERK 1/2 phosphorylation due to high FFAs. All these results indicated that evodiamine could correct the upregulated expression of P2X7 receptor induced under high FFA condition in HUVECs, and consequently suppressed oxidative stress and inflammatory responses.

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