HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia

Su, Jingjing; Zhou, Houguang; Tao, Yong; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Ying; Tang, Yuping; Hu, Renming; Dong, Qiang

doi:10.1016/j.cellsig.2014.10.003

Cited by 9 publications

(4 citation statements)

References 33 publications

(49 reference statements)

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“…Oxygen sensing is a property of essentially all cell types, and the response to hypoxia is multidimensional, involving complicated intracellular signal transduction networks (Semenza, 2001; Cummins and Taylor, 2005; Kaelin and Ratcliffe, 2008). Under limiting oxygen concentration, at the organismal level, others and we have observed fetal growth restriction (Goyal et al, 2011), and at the cellular level reduced viability (Su et al, 2015). Under hypoxic condition, cells undergo several changes to survive, and dysregulation of these changes makes them vulnerable to death (Zou et al, 2014).…”

Section: Introductionmentioning

confidence: 63%

Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

Mata‐Greenwood

Goyal

2017

Front. Physiol.

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Background : Hypoxia inducible factor 1 alpha (HIF1A) is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen) on human brain micro endothelial cells (HBMEC) viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

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Section: Introductionmentioning

confidence: 63%

Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

Mata‐Greenwood

Goyal

2017

Front. Physiol.

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“…Few studies have looked at these molecules when investigating the effect of PUFAs on endothelial cell proliferation. Su et al [ 29 ] showed high concentrations of free fatty acids affect the expression of cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, p53, and cell division cycle protein 14 in human brain vascular endothelial cells, although the fatty acid composition of their treatment was not specified. Artwohl et al [ 14 ] showed a correlation between an increase in the expression of p21 (inhibitor of cyclin-dependent kinase), a decrease of cyclin D3 protein expression, an increased number of cells in G 0 /G 1 phase, and a decreased number of cells in S phase when they reported LA and AA caused cell cycle arrest in HUVECs, and suggested a sophisticated cell cycle controlling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Importance of extracellular matrix and growth state for the EA.hy926 endothelial cell response to polyunsaturated fatty acids

Taylor

Aukema

et al. 2018

PLoS ONE

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Consumption of different PUFAs (polyunsaturated fatty acids) can induce functional changes in blood vessels via endothelial cells, which interact with dietary factors in the circulation. The basement membrane that separates the endothelium from the smooth muscle cells of the medial layer can also influence the functional state of endothelial cells. However, the effect of basement membrane on the endothelial response to dietary PUFAs in relation to growth state (e.g. proliferation versus quiescence) has never been investigated. We therefore compared the viability (CCK kit) and proliferation (bromodeoxyuridine incorporation) of EA.hy926 endothelial cells grown on Matrigel or collagen versus non-coated plates. EA.hy926 viability and proliferation were also assessed after treatment with 0–150 μM of PUFAs [linoleic acid (LA), arachidonic acid (AA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. Our study showed that only cells grown on Matrigel-coated plates reached quiescence after becoming confluent with a decreased level of MCM2 and p-cyclin D1 (T286), increased levels of p27kip1 and a low level of apoptosis and senescence. AA, EPA and DHA decreased the viability and proliferation of subconfluent cells grown on plastic dishes in a dose-dependent manner, while the presence of Matrigel made the cells resistant to these adverse effects. Confluent cell viability was less sensitive to higher concentrations of AA, EPA and DHA than subconfluent cells, and a significant increase in caspase-3 cleavage was only observed in confluent cells treated with DHA. Higher concentrations of AA, EPA and DHA suppressed DNA synthesis by both subconfluent and confluent cells, while precursor C18 PUFAs (LA and ALA) had no negative effects on viability and proliferation. Our study is the first to show that extracellular matrix and growth state are important factors in the EA.hy926 cell response to PUFAs, and that the mechanisms by which individual PUFAs operate may be growth state-dependent.

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“…Detachment and apoptosis of endothelial cells are associated phenomena (Endemann and Schiffrin, ). Cell cycle arrest has been intimately linked with endothelial dysfunction due to the influence of cell progression (Su et al, ). Therefore, endothelial dysfunction is a hallmark of vascular diseases and has also been shown to be predictive of adverse cardiovascular events (Tang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

Guo

et al. 2015

Environ. Toxicol.

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Endosulfan is one of the organochlorine pesticides. It has been associated with a wide range of adverse health effects. However, it is unknown whether endosulfan causes endothelial dysfunction. In the present study, we investigated the effects of endosulfan on human vascular endothelial cells. We exposed human umbilical vein endothelial cells (HUVEC-C) to varying concentrations of endosulfan for 48 h. The results showed that endosulfan lowered cell viability and inhibited cell proliferation in a dose-dependent manner. Flow cytometric analysis showed that endosulfan at 60 μM induced G1 cell cycle arrest, a response attributed to down-regulation of CDK6 and pRb dephosphorylation. We observed that endosulfan at 40 and 60 μM induced a considerable percentage of cells to undergo apoptosis, as detected by Annexin-V binding assays. Endosulfan reduced mitochondrial transmembrane potential, leading to the release of cytochrome c into the cytoplasm; meanwhile, endosulfan also inhibited the mRNA expression level of survivin, which resulted in the activation of caspase-3. These results indicated that the intrinsic mitochondria-mediated pathway was involved in apoptotic process. Exposure to endosulfan increased the secretion and mRNA expression levels of inflammation factors interleukin (IL)-6 and IL-8, suggesting that endosulfan could cause inflammation. Overall, these findings suggested that endosulfan is toxic to HUVEC-C cells, resulting in endothelial dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1785-1795, 2016.

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HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia

Cited by 9 publications

References 33 publications

Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

Importance of extracellular matrix and growth state for the EA.hy926 endothelial cell response to polyunsaturated fatty acids

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

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