Lipid mediators of autophagy in stress-induced premature senescence of endothelial cells

2008 ◽  
Vol 294 (3) ◽  
pp. H1119-H1129 ◽  
Author(s):  
Susann Patschan ◽  
Jun Chen ◽  
Alla Polotskaia ◽  
Natalja Mendelev ◽  
Jennifer Cheng ◽  
...  

Our group (Patschan S, Chen J, Gealekman O, Krupincza K, Wang M, Shu L, Shayman JA, Goligorsky MS; Am J Physiol Renal Physiol 294: F100–F109, 2008) previously observed an accumulation of gangliosides coincident with development of cell senescence and demonstrated lysosomal permeabilization in human umbilical vein endothelial cells exposed to glycated collagen I (GC). Therefore, we investigated whether the lysosome-dependent, caspase-independent or type 2-programmed cell death (autophagy) is involved in development of premature senescence of endothelial cells. The cleaved microtubule-associated protein 1 light-chain 3 (LC3), a marker of autophagosome formation, was overexpressed within 24 h of GC treatment; however, by 4–5 days, it was nearly undetectable. Early induction of autophagosomes was associated with their fusion with lysosomes, a phenomenon that later became subverted. Autophagic cell death can be triggered by the products of damaged plasma membrane, sphingolipids, and ceramide. We observed a clustering of membrane rafts shortly after exposure to GC; later, after 24 h, we observed an internalization, accompanied by an increased acid sphingomyelinase activity and accumulation of ceramide. Pharmacological inhibition of autophagy prevented development of premature senescence but did lead to the enhanced rate of apoptosis in human umbilical vein endothelial cells exposed to GC. Pharmacological induction of autophagy resulted in reciprocal changes. These observations appear to represent a mechanistic molecular cascade whereby advanced glycation end products like GC induce sphingomyelinase activity, accumulation of ceramide, clustering, and later internalization of lipid rafts.

Heart ◽  
2013 ◽  
Vol 99 (Suppl 3) ◽  
pp. A48.1-A48
Author(s):  
Song Zhiming ◽  
Hao Baoshun ◽  
Liu Yong ◽  
Liu Dinghui ◽  
Qian Xiaoxian

2021 ◽  
Vol 9 ◽  
pp. 205031212110268
Author(s):  
Samar Sultan

Objectives: This study reports the levels of cytokines, chemokines, and growth factors previously identified as taking part in the pathology of atherosclerosis in human umbilical vein endothelial cells derived from mothers with type 2 diabetes and compares them with those in human umbilical vein endothelial cells derived from healthy mothers under normal glucose conditions. Methods: Cytokine analysis measures of human umbilical vein endothelial cell lysates were obtained using a multiple analyte profiling (xMAP) assay based on magnetic bead-based technology, using the MAGPIX instrument. The correlation between cytokines, chemokines, and growth factors was examined statistically in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Results: This study showed that the expression of proinflammatory cytokine interleukin-1 alpha was significantly greater in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. The protein level of granulocyte colony-stimulating factor was higher in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. A significant positive correlation was demonstrated between the protein expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in human umbilical vein endothelial cells derived from mothers with type 2 diabetes. Conclusion: Diabetes evokes a persistent inflammatory phenotype in human umbilical vein endothelial cells, as indicated by the enhanced production of cytokines and growth factors under normal glucose conditions.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Jipeng Ouyang ◽  
Rong Li ◽  
Haiqin Shi ◽  
Jianping Zhong

Migraine is a prevalent neurological disorder which causes a huge economic burden on society. It is thought to be a neurovascular disease with oxidative stress might be involved. Curcumin, one of the major ingredients of turmeric, has potent antioxidative and anti-inflammatory properties, but whether it could be used as a potential treatment for migraine remains to be explored. In the present study, human umbilical vein endothelial cells (HUVECs) were pretreated with various concentrations of curcumin (0 μM, 10 μM, 20 μM, 30 μM, 40 μM, and 50 μM) for 12 h, thereby exposed to H2O2 (100 μM) for another 12 h. The viability of HUVECs was tested by the CCK-8 assay, and the activities of antioxidant enzymes including superoxide dismutase (SOD) and glutathione (GSH) were also examined. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) were assayed to determine H2O2-induced oxidative stress. In addition, several cell death-related genes (p53, p21, Bax, and Bcl-2) were detected by PCR, and an apoptosis-related protein (caspase3) was evaluated by western blotting. Our results showed that curcumin improved the H2O2-induced decrease of cell viability and antioxidative enzyme activities and decreased the level of oxidative stress. As a conclusion, curcumin could mitigate H2O2-induced oxidative stress and cell death in HUVECs and may be a potential therapeutic drug for migraine.


1998 ◽  
Vol 56 (12) ◽  
pp. 1615-1624 ◽  
Author(s):  
Bernd Lorenz ◽  
Thomas Schlüter ◽  
Ralf Bohnensack ◽  
Gabriela Pergande ◽  
Werner E.G Müller

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