Heat Shock Induces IκB-α and Prevents Stress-Induced Endothelial Cell Apoptosis

DeMeester, Susan L.; Buchman, Timothy G.; Qiu, Yinsheng; Jacob, Ammini K.; Dunnigan, Keith; Hotchkiss, Richard S.; Karl, Irene E.; Cobb, J. Perren

doi:10.1001/archsurg.1997.01430360029005

Cited by 62 publications

(55 citation statements)

References 16 publications

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“…One hour after a nonlethal heat shock treatment, cells no longer responded to added cytokines, as evidenced by the significant reduction in p50/p65 DNA binding, and suppression of NF-Bdriven reporter enzyme activity. As was shown in this study and previously by others (3,8,29,30), cells after stress failed to phosphorylate and subsequently degrade IB␣, the result being a failure of p50/p65 to translocate to the nucleus and bind to and stimulate the expression of genes normally activated following cytokine stimulation.…”

Section: Discussionsupporting

confidence: 80%

Stress-Induced Inhibition of the NF-κB Signaling Pathway Results from the Insolubilization of the IκB Kinase Complex following Its Dissociation from Heat Shock Protein 90

Pittet

Lee

Pespeni

et al. 2005

The Journal of Immunology

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Activation of the stress response attenuates proinflammatory responses by suppressing cytokine-stimulated activation of the NF-κB signaling pathway. In this study, we show that the activation of the cellular stress response, either by heat shock treatment or after exposure to sodium arsenite, leads to a transient inhibition of IκBα phosphorylation. Inhibition of IκBα phosphorylation after stress was associated with the detergent insolubilization of the upstream kinases, IκB kinase α (IKKα) and IκB kinase β, components involved in IκBα phosphorylation. Pretreatment of cells with glycerol, a chemical chaperone that reduces the extent of stress-induced protein denaturation, reduced the stress-dependent detergent insolubility of the IKK complex and restored the cytokine-stimulated phosphorylation of IκB. The stress-dependent insolubility of the IKK complex appeared reversible; as the cells recovered from the heat shock treatment, the IKK complex reappeared within the soluble fraction of cells and was again capable of mediating the phosphorylation of IκBα in response to added cytokines. Treatment of cells with geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) function, also resulted in IKK detergent insolubility and proteasome-mediated degradation of the IKK complex. Furthermore, while IKKα coprecipitated with Hsp90 in control cells, coprecipitation of the two proteins was greatly reduced in those cells early after stress or following exposure to geldanamycin. Stress-induced transient insolubilization of the IκB kinase complex following its dissociation from Hsp90 represents a novel mechanism by which the activation of the stress response inhibits the NF-κB signaling pathway in response to proinflammatory stimuli.

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Section: Discussionsupporting

confidence: 80%

Stress-Induced Inhibition of the NF-κB Signaling Pathway Results from the Insolubilization of the IκB Kinase Complex following Its Dissociation from Heat Shock Protein 90

Pittet

Lee

Pespeni

et al. 2005

The Journal of Immunology

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“…Previous studies have used one or both of these cytotoxicity assays and/or the differential dye uptake assay in combination with other assay methods (Edwards and Tolkovsky, 1994;Hardwick et al;Hughes et al, 1996;Burger et al, 1999;Lizard et al, 1999;McGuinness et al, 1999;Sumitomo et al, 1999;DeMeester et al, 1997). However, none have used this specific combination of assays in evaluating apoptosis in breast cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Staurosporine-induced apoptosis and hydrogen peroxide-induced necrosis in two human breast cell lines

2003

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The use of apoptosis-inducing agents in the treatment of malignant cancer is increasingly being considered as a therapeutic approach. In this study, the induction of apoptosis and necrosis was examined in terms of temporal dose responses, comparing a malignant and nonmalignant breast cell line. Staurosporine (SSP)-induced apoptosis and H 2 O 2 -induced necrosis were evaluated by two cytotoxicity assays, neutral red (NR) and methyl-thiazolyl tertrazolium (MTT), in comparison with a differential dye uptake assay, using Hoechst33342/propidium iodide (Hoechst/PI). Confirmatory morphological assessment was also performed by routine resin histology and transmission electron microscopy. Cell viability was assessed over a 0.5 -48 h time course. In nonmalignant HBL-100 cells, 50 nM SSP induced 100% apoptosis after a 48 h exposure, while the same exposure to SSP caused only 4% apoptosis in metastatic T47D cells. Although complete apoptosis of both cell lines was induced by 50 mM SSP, this effect was delayed in T47D (24 h) compared with HBL-100 (4 h). Results also showed that neither MTT or NR can distinguish between the modes of cell death, nor detect the early onset of apoptosis revealed by Hoechst/PI.

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“…Hernan dez-Presa et al 16 have also demonstrated NF-B activation in early atherosclerosis. Other studies have shown a critical role of NF-B activation in myocardial 26 and endothelial cell 17 apoptosis. Some studies have also shown NF-B as a proapoptotic signal in human endothelial cells.…”

Section: Lox-1 and Nf-b Signal Transductionmentioning

confidence: 91%

“…14,15 Previous studies have demonstrated that NF-B is activated in accelerated and in advanced atherosclerosis. 16 Recent studies show that NF-B activation plays a critical role in apoptosis 17,18 and that ox-LDL induces the activation of NF-B in fibroblasts and in endothelial and smooth muscle cells. 19 Accordingly, we hypothesized that (1) ox-LDL upregulates its own receptor, LOX-1; (2) ox-LDL-mediated apoptosis of cultured HCAECs is associated with the action of LOX-1; and (3) NF-B activation plays an important role in this process.…”

mentioning

confidence: 99%

Upregulation of Endothelial Receptor for Oxidized LDL (LOX-1) by Oxidized LDL and Implications in Apoptosis of Human Coronary Artery Endothelial Cells

Mehta

2000

ATVB

317

256

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Abstract-A specific lectinlike endothelial receptor for oxidized low density lipoprotein (LOX-1), distinct from the scavenger receptor in monocytes/macrophages, has been identified and cloned. In this study, we examined the regulation of LOX-1 by oxidized low density lipoprotein (ox-LDL) and determined the role of LOX-1 in ox-LDL-induced apoptosis of cultured human coronary artery endothelial cells (HCAECs). Incubation of HCAECs with ox-LDL (40 g/mL), but not native LDL, for 24 hours markedly increased LOX-1 expression (mRNA and protein). After 48 hours of preincubation of HCAECs with a specific antisense to LOX-1 mRNA (antisense LOX-1), ox-LDL-mediated upregulation of LOX-1 was suppressed (PϽ0.01). In contrast, treatment of HCAECs with sense LOX-1 had no effect. Recent studies show that cytokine tumor necrosis factor (TNF)-␣ 4 and fluid shear stress 5 markedly upregulate LOX-1 gene expression in endothelial cells. Another study 6 has shown that LOX-1 expression is dramatically increased in hypertensive rats. A more recent study from our laboratory 7 has demonstrated that angiotensin II upregulates LOX-1 expression as well as the uptake of ox-LDL in human coronary artery endothelial cells (HCAECs).It is widely appreciated that LDL, especially its oxidatively modified form (ox-LDL), is a critical factor in atherogenesis.Endothelial dysfunction elicited by ox-LDL has been identified in the course of atherogenesis and its complications. 8 LDL is oxidized in vascular endothelial cells to a highly injurious product that results in characteristic cell dysfunction in large arteries and resistant vessels. Endothelial dysfunction (ie, loss of vasodilation, vasoconstriction, thrombosis, and inflammation) occurs before and throughout the development of atherosclerosis and particularly during plaque rupture. Ox-LDL appears to induce this cellular dysfunction in a timeand concentration-dependent manner. 9 Recent studies show that apoptosis, which is a common accompaniment of atherosclerosis, is induced by ox-LDL in cultured vascular smooth muscle cells, 10 monocytes/macrophages, 11 and human endothelial cells. 12 The mechanisms of ox-LDL-mediated apoptosis, particularly in endothelial cells, and of its relation with LOX-1 have not been defined.Nuclear factor (NF)-B, a transcription factor, regulates the transcription of a variety of cellular genes, including injury response and growth control. 13 Activation of NF-B is

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Heat Shock Induces IκB-α and Prevents Stress-Induced Endothelial Cell Apoptosis

Cited by 62 publications

References 16 publications

Stress-Induced Inhibition of the NF-κB Signaling Pathway Results from the Insolubilization of the IκB Kinase Complex following Its Dissociation from Heat Shock Protein 90

Stress-Induced Inhibition of the NF-κB Signaling Pathway Results from the Insolubilization of the IκB Kinase Complex following Its Dissociation from Heat Shock Protein 90

Staurosporine-induced apoptosis and hydrogen peroxide-induced necrosis in two human breast cell lines

Upregulation of Endothelial Receptor for Oxidized LDL (LOX-1) by Oxidized LDL and Implications in Apoptosis of Human Coronary Artery Endothelial Cells

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