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Conference Paper: Intermittent hypoxia enhances inflammation and oxidative stress in Eahy926 endothelial cells via suppression of HO-1 expression
Title | Intermittent hypoxia enhances inflammation and oxidative stress in Eahy926 endothelial cells via suppression of HO-1 expression |
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Authors | |
Keywords | Medical sciences Respiratory diseases |
Issue Date | 2011 |
Publisher | American Thoracic Society. The Conference Abstracts' web site is located at http://www.atsjournals.org/series/ajrccm-conference |
Citation | The 2011 International Conference of the American Thoracic Society (ATS), Denver, CO., 13-18 May 2011. In American Journal of Respiratory and Critical Care Medicine, 2011, v. 183 meeting abstracts, abstract no. A2475 How to Cite? |
Abstract | RATIONALE: Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA), which is increasingly recognized as an independent risk factor of atherosclerosis. Although the underlying mechanisms have not been fully understood, inflammation and oxidative stress have been suggested as major pathological events initiating or accelerating atherogenesis. Heme oxygenase-1 (HO-1) plays a regulatory role in the inflammatory response by modulating production of pro-inflammatory cytokines, and its expression is mediated by nuclear translocation of nuclear factor, erythroid 2 related factor 2 (Nrf-2), a transcription factor in response to oxidative stress. This study was to address whether IH would upregulate the expression of pro-inflammatory cytokines via HO-1 expression in endothelial cells in vitro. METHODS: EAhy 926 cells were exposed to intermittent normoxia (IN as control) or IH [a 10-min hypoxia (5% O2) followed by a 5-min normoxia (21% O2) for 64 cycles using the BioSpherix OxyCycler C42 system (BioSpherix, Redfield, NY)]. IL-6 and IL-8 mRNA expressions were measured by RT-PCR, and protein secreted was measured by ELISA. Cellular activities of GSH-related enzymes such as glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed. Whole cell lysates, cytosolic and nuclear fractions were extracted to perform Western blot for HO-1, Nrf-2, and phospho-ERK. RESULTS: IH increased the production of IL-6 and IL-8 protein without changing the mRNA levels. IH also enhanced the enzyme activities of GPx and GR. On the other hand, IH suppressed HO-1 and Nrf-2 expression, accompanied by the inhibition of ERK phosphorylation. CONCLUSIONS: These data suggest an underlying mechanism for OSA subjects predisposed to atherosclerosis and a potential role of HO-1 in the therapeutic therapy of OSA-related atherosclerosis. |
Description | Poster Discussion Session - A109 Hypoxia |
Persistent Identifier | http://hdl.handle.net/10722/137792 |
ISSN | 2021 Impact Factor: 30.528 2020 SCImago Journal Rankings: 6.272 |
DC Field | Value | Language |
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dc.contributor.author | Han, Q | en_US |
dc.contributor.author | Yeung, SC | en_US |
dc.contributor.author | Ip, MSM | en_US |
dc.contributor.author | Mak, JCW | en_US |
dc.date.accessioned | 2011-08-26T14:33:27Z | - |
dc.date.available | 2011-08-26T14:33:27Z | - |
dc.date.issued | 2011 | en_US |
dc.identifier.citation | The 2011 International Conference of the American Thoracic Society (ATS), Denver, CO., 13-18 May 2011. In American Journal of Respiratory and Critical Care Medicine, 2011, v. 183 meeting abstracts, abstract no. A2475 | en_US |
dc.identifier.issn | 1073-449X | - |
dc.identifier.uri | http://hdl.handle.net/10722/137792 | - |
dc.description | Poster Discussion Session - A109 Hypoxia | - |
dc.description.abstract | RATIONALE: Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA), which is increasingly recognized as an independent risk factor of atherosclerosis. Although the underlying mechanisms have not been fully understood, inflammation and oxidative stress have been suggested as major pathological events initiating or accelerating atherogenesis. Heme oxygenase-1 (HO-1) plays a regulatory role in the inflammatory response by modulating production of pro-inflammatory cytokines, and its expression is mediated by nuclear translocation of nuclear factor, erythroid 2 related factor 2 (Nrf-2), a transcription factor in response to oxidative stress. This study was to address whether IH would upregulate the expression of pro-inflammatory cytokines via HO-1 expression in endothelial cells in vitro. METHODS: EAhy 926 cells were exposed to intermittent normoxia (IN as control) or IH [a 10-min hypoxia (5% O2) followed by a 5-min normoxia (21% O2) for 64 cycles using the BioSpherix OxyCycler C42 system (BioSpherix, Redfield, NY)]. IL-6 and IL-8 mRNA expressions were measured by RT-PCR, and protein secreted was measured by ELISA. Cellular activities of GSH-related enzymes such as glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed. Whole cell lysates, cytosolic and nuclear fractions were extracted to perform Western blot for HO-1, Nrf-2, and phospho-ERK. RESULTS: IH increased the production of IL-6 and IL-8 protein without changing the mRNA levels. IH also enhanced the enzyme activities of GPx and GR. On the other hand, IH suppressed HO-1 and Nrf-2 expression, accompanied by the inhibition of ERK phosphorylation. CONCLUSIONS: These data suggest an underlying mechanism for OSA subjects predisposed to atherosclerosis and a potential role of HO-1 in the therapeutic therapy of OSA-related atherosclerosis. | - |
dc.language | eng | en_US |
dc.publisher | American Thoracic Society. The Conference Abstracts' web site is located at http://www.atsjournals.org/series/ajrccm-conference | - |
dc.relation.ispartof | American Journal of Respiratory and Critical Care Medicine | en_US |
dc.subject | Medical sciences | - |
dc.subject | Respiratory diseases | - |
dc.title | Intermittent hypoxia enhances inflammation and oxidative stress in Eahy926 endothelial cells via suppression of HO-1 expression | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1073-449X&volume=183&issue=Meeting Abstracts&spage=abstract no. A2475&epage=&date=2011&atitle=Intermittent+hypoxia+enhances+inflammation+and+oxidative+stress+in+Eahy926+endothelial+cells+via+suppression+of+HO-1+expression | - |
dc.identifier.email | Yeung, SC: flag@hkucc.hku.hk | en_US |
dc.identifier.email | Ip, MSM: msmip@hku.hk | en_US |
dc.identifier.email | Mak, JCW: judithmak@hku.hk | en_US |
dc.identifier.authority | Ip, MSM=rp00347 | en_US |
dc.identifier.authority | Mak, JCW=rp00352 | en_US |
dc.identifier.hkuros | 191799 | en_US |
dc.identifier.volume | 183 | - |
dc.identifier.issue | meeting abstracts | - |
dc.description.other | The 2011 International Conference of the American Thoracic Society (ATS), Denver, CO., 13-18 May 2011. In American Journal of Respiratory and Critical Care Medicine, 2011, v. 183 (Meeting Abstracts), abstract no. A2475 | - |
dc.identifier.issnl | 1073-449X | - |