| Differential effects of hypoxic stress in alveolar epithelial cells and microvascular endothelial cells. | |
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MedLine Citation:
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PMID: 20054152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Under hypoxic conditions eukaryotic cells and tissues undergo adaptive responses involving glycolysis, angiogenesis, vasoconstriction and inflammation. The underlying molecular mechanisms are not yet fully elucidated and are most likely cell and tissue specific. In the lung, alveolar epithelial cells and microvascular endothelial cells are highly sensitive to hypoxia and together orchestrate a rapid and sustained adaptive response. We examined the effect of different oxygen tensions on cell viability, glucose metabolism, key transcription factors and signaling molecules, in alveolar epithelial cells (A549) and microvascular endothelial cells (HMEC-1). Both cell types tolerated hypoxia without detectable cell injury. Hypoxia induced glycolysis in both epithelial and microvascular endothelial cells, although A549 cells exhibited a higher rate of glucose consumption. The transcription factor CREB (cAMP response element binding protein) was activated with decreasing oxygen tensions in both cell types. This effect was again more marked in A549 cells, demonstrating epithelial cells to be more oxygen sensitive. Activating Transcription Factor 3 (ATF-3) was heavily induced by hypoxia in A549 cells but not in HMEC-1 cells. Both cell types exhibited hypoxia induced secretion of VEGF and IL-6. Secretion of the vasoconstrictor endothelin-1 (ET1) was increased by hypoxia in HMEC-1 cells but decreased in A549 cells. These data reveal that both cell types exhibit an adaptive response to hypoxia but alveolar epithelial cells are generally more sensitive. ET-1 was oppositely regulated by decreased oxygen tensions in the investigated cell types. The present study further elucidates the adaptive molecular mechanisms in pulmonary hypoxia and demonstrates cell specific responses. |
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Authors:
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Sara Signorelli; Paul Jennings; Martin O Leonard; Walter Pfaller |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-22 |
Journal Detail:
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Title: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Volume: 25 ISSN: 1421-9778 ISO Abbreviation: Cell. Physiol. Biochem. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-01-07 Completed Date: 2010-02-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9113221 Medline TA: Cell Physiol Biochem Country: Switzerland |
Other Details:
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Languages: eng Pagination: 135-44 Citation Subset: IM |
Copyright Information:
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2010 S. Karger AG, Basel |
Affiliation:
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Innsbruck Medical University, Division of Physiology, Department of Physiology and Medical Physics, Innsbruck, Austria. Sara.Signorelli@i-med.ac.at |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Activating Transcription Factor 3
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genetics,
metabolism Cell Hypoxia* Cell Line Cell Line, Tumor Cell Membrane / metabolism Cell Survival* Cyclic AMP Response Element-Binding Protein / metabolism Endothelin-1 / metabolism Endothelium, Vascular / cytology*, metabolism Gene Expression Glucose / metabolism Humans Interleukin-6 / metabolism Microvessels / cytology* Oxygen / metabolism* Pneumocytes / cytology*, metabolism RNA, Messenger / genetics Vascular Endothelial Growth Factor A / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Activating Transcription Factor 3; 0/Cyclic AMP Response Element-Binding Protein; 0/Endothelin-1; 0/Interleukin-6; 0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; 50-99-7/Glucose; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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