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Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length
Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation. Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respi...
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Published in: | American journal of physiology. Lung cellular and molecular physiology 2023-03, Vol.324 (3), p.L325-L334 |
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container_title | American journal of physiology. Lung cellular and molecular physiology |
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creator | Teape, Daniella Peterson, Abigail Ahsan, Nagib Ellis, Kimberlyn Correia, Nicholas Luo, Ryan Hegarty, Katy Yao, Hongwei Dennery, Phyllis |
description | Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation. Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice ( |
doi_str_mv | 10.1152/ajplung.00522.2021 |
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Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice (<12 h old) were exposed to hyperoxia for 72 h and recovered in room air until postnatal day (PND) 60. Cilia length was measured from scanning electron microscopy images using a MATLAB-derived program. Proteomics and metabolomics were carried out in cells after hyperoxia. After hyperoxia, there was a significant time-dependent reduction in cilia length after hyperoxia in HAEC. Proteomic analysis showed decreased abundance of multiple proteins related to IFT including dynein motor proteins. In neonatal mice exposed to hyperoxia, there was a significant decrease in acetylated α tubulin at PND10 followed by recovery to normal levels at PND60. In HAEC, hyperoxia decreased the abundance of multiple proteins associated with complex I of the electron transport chain. In HAEC, hyperoxia increased levels of malate, fumarate, and citrate, and reduced the ATP/ADP ratio at 24 h with a subsequent increase at 36 h. Exposure to hyperoxia reduced cilia length, and this was associated with aberrant IFT protein expression and dysregulated metabolism. This suggests that hyperoxic exposure leads to aberrant IFT protein expression in the respiratory epithelium resulting in shortened cilia.</description><identifier>ISSN: 1040-0605</identifier><identifier>EISSN: 1522-1504</identifier><identifier>DOI: 10.1152/ajplung.00522.2021</identifier><identifier>PMID: 36719084</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Biological Transport ; Cilia - metabolism ; Dyneins ; Humans ; Hyperoxia - metabolism ; Lung - metabolism ; Mice ; Proteins - metabolism ; Proteomics</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 2023-03, Vol.324 (3), p.L325-L334</ispartof><rights>Copyright © 2023 the American Physiological Society. 2023 American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c309t-8c003ced035d5be4213fd7dbe77d1e4bf62945ad5a9ecd37dc2c74a7938eec453</cites><orcidid>0000-0003-0948-0111 ; 0000-0001-5745-1855 ; 0000-0002-1809-5613 ; 0000-0001-7033-897X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36719084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teape, Daniella</creatorcontrib><creatorcontrib>Peterson, Abigail</creatorcontrib><creatorcontrib>Ahsan, Nagib</creatorcontrib><creatorcontrib>Ellis, Kimberlyn</creatorcontrib><creatorcontrib>Correia, Nicholas</creatorcontrib><creatorcontrib>Luo, Ryan</creatorcontrib><creatorcontrib>Hegarty, Katy</creatorcontrib><creatorcontrib>Yao, Hongwei</creatorcontrib><creatorcontrib>Dennery, Phyllis</creatorcontrib><title>Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><description>Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation. Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice (<12 h old) were exposed to hyperoxia for 72 h and recovered in room air until postnatal day (PND) 60. Cilia length was measured from scanning electron microscopy images using a MATLAB-derived program. Proteomics and metabolomics were carried out in cells after hyperoxia. After hyperoxia, there was a significant time-dependent reduction in cilia length after hyperoxia in HAEC. Proteomic analysis showed decreased abundance of multiple proteins related to IFT including dynein motor proteins. In neonatal mice exposed to hyperoxia, there was a significant decrease in acetylated α tubulin at PND10 followed by recovery to normal levels at PND60. In HAEC, hyperoxia decreased the abundance of multiple proteins associated with complex I of the electron transport chain. In HAEC, hyperoxia increased levels of malate, fumarate, and citrate, and reduced the ATP/ADP ratio at 24 h with a subsequent increase at 36 h. Exposure to hyperoxia reduced cilia length, and this was associated with aberrant IFT protein expression and dysregulated metabolism. This suggests that hyperoxic exposure leads to aberrant IFT protein expression in the respiratory epithelium resulting in shortened cilia.</description><subject>Animals</subject><subject>Biological Transport</subject><subject>Cilia - metabolism</subject><subject>Dyneins</subject><subject>Humans</subject><subject>Hyperoxia - metabolism</subject><subject>Lung - metabolism</subject><subject>Mice</subject><subject>Proteins - metabolism</subject><subject>Proteomics</subject><issn>1040-0605</issn><issn>1522-1504</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpVkUtv1DAUhS1ERdspf4AF8pJNhms7HicbJFQVilSJTbu2HPsm48p5YDvQ-fd46FDBxg_dc8-1z0fIOwZbxiT_aB6XsE7DFkByvuXA2StyUQq8YhLq1-UMNVSwA3lOLlN6hCIE2L0h52KnWAtNfUHS7WHBOD95Q_24GB8T9VOOpg9mwBBMpOUypWWOmZrJUWvWhIm6Q4o4rMFkdHTEbLo5-DTSXz7vacS0hmymTB3aiCYVjfWhjAg4DXl_Rc56ExK-Pe0b8vDl5v76trr7_vXb9ee7ygpoc9VYAGHRgZBOdlhzJnqnXIdKOYZ11-94W0vjpGnROqGc5VbVRrWiQbS1FBvy6dl3WbsRncXjx4Jeoh9NPOjZeP1_ZfJ7Pcw_dds2TYmxGHw4GcT5x4op69Ene4xlwnlNmivFhOCsrBvCn6U2zqlk07-MYaCPtPSJlv5DSx9plab3_z7wpeUvHvEbnbqX2A</recordid><startdate>20230301</startdate><enddate>20230301</enddate><creator>Teape, Daniella</creator><creator>Peterson, Abigail</creator><creator>Ahsan, Nagib</creator><creator>Ellis, Kimberlyn</creator><creator>Correia, Nicholas</creator><creator>Luo, Ryan</creator><creator>Hegarty, Katy</creator><creator>Yao, Hongwei</creator><creator>Dennery, Phyllis</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0948-0111</orcidid><orcidid>https://orcid.org/0000-0001-5745-1855</orcidid><orcidid>https://orcid.org/0000-0002-1809-5613</orcidid><orcidid>https://orcid.org/0000-0001-7033-897X</orcidid></search><sort><creationdate>20230301</creationdate><title>Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length</title><author>Teape, Daniella ; Peterson, Abigail ; Ahsan, Nagib ; Ellis, Kimberlyn ; Correia, Nicholas ; Luo, Ryan ; Hegarty, Katy ; Yao, Hongwei ; Dennery, Phyllis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-8c003ced035d5be4213fd7dbe77d1e4bf62945ad5a9ecd37dc2c74a7938eec453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Biological Transport</topic><topic>Cilia - metabolism</topic><topic>Dyneins</topic><topic>Humans</topic><topic>Hyperoxia - metabolism</topic><topic>Lung - metabolism</topic><topic>Mice</topic><topic>Proteins - metabolism</topic><topic>Proteomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teape, Daniella</creatorcontrib><creatorcontrib>Peterson, Abigail</creatorcontrib><creatorcontrib>Ahsan, Nagib</creatorcontrib><creatorcontrib>Ellis, Kimberlyn</creatorcontrib><creatorcontrib>Correia, Nicholas</creatorcontrib><creatorcontrib>Luo, Ryan</creatorcontrib><creatorcontrib>Hegarty, Katy</creatorcontrib><creatorcontrib>Yao, Hongwei</creatorcontrib><creatorcontrib>Dennery, Phyllis</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teape, Daniella</au><au>Peterson, Abigail</au><au>Ahsan, Nagib</au><au>Ellis, Kimberlyn</au><au>Correia, Nicholas</au><au>Luo, Ryan</au><au>Hegarty, Katy</au><au>Yao, Hongwei</au><au>Dennery, Phyllis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><date>2023-03-01</date><risdate>2023</risdate><volume>324</volume><issue>3</issue><spage>L325</spage><epage>L334</epage><pages>L325-L334</pages><issn>1040-0605</issn><eissn>1522-1504</eissn><abstract>Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation. Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice (<12 h old) were exposed to hyperoxia for 72 h and recovered in room air until postnatal day (PND) 60. Cilia length was measured from scanning electron microscopy images using a MATLAB-derived program. Proteomics and metabolomics were carried out in cells after hyperoxia. After hyperoxia, there was a significant time-dependent reduction in cilia length after hyperoxia in HAEC. Proteomic analysis showed decreased abundance of multiple proteins related to IFT including dynein motor proteins. In neonatal mice exposed to hyperoxia, there was a significant decrease in acetylated α tubulin at PND10 followed by recovery to normal levels at PND60. In HAEC, hyperoxia decreased the abundance of multiple proteins associated with complex I of the electron transport chain. In HAEC, hyperoxia increased levels of malate, fumarate, and citrate, and reduced the ATP/ADP ratio at 24 h with a subsequent increase at 36 h. Exposure to hyperoxia reduced cilia length, and this was associated with aberrant IFT protein expression and dysregulated metabolism. 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subjects | Animals Biological Transport Cilia - metabolism Dyneins Humans Hyperoxia - metabolism Lung - metabolism Mice Proteins - metabolism Proteomics |
title | Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length |
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