Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation
Inhibition of the nuclear enzyme poly ribose synthetase (PARS) protects against in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to character...
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| Veröffentlicht in: | Experimental and molecular pathology 2008-04, Vol.84 (2), p.141-144 |
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| creator | McCourtie, Anton S. Farivar, Alexander S. Woolley, Steven M. Merry, Heather E. Wolf, Patrick S. Szabo, Csaba Mulligan, Michael S. |
| description | Inhibition of the nuclear enzyme poly ribose synthetase (PARS) protects against
in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to characterize the effects of PARS on AM activation in response to oxidative stress.
Primary cultures of AM were rendered hypoxic for 2 h and reoxygenated for up to 4 h. Cells were preincubated with INO-1001, a specific PARS inhibitor 1 h prior to hypoxia. Gel shift assays characterized nuclear factor kappa B (NFκB), and enzyme linked immunosorbent assay quantitated chemokine/cytokine protein secretion.
Hypoxia and reoxygenation resulted in an increase in the early nuclear translocation of NFκB, and an increase in the secretion of the cytokine tumor necrosis factor-alpha (TNF-α), chemokines macrophage inflammatory protein (MIP-1α), monocyte chemoattractant protein one (MCP-1) and cytokine induced neutrophil chemoattractant (CINC). Pretreatment of AM with INO-1001 decreased both the early translocation of NFκB and the production of TNF-α (
p
<
0.05) and MIP-1α
p
=
0.02, but did not affect CINC or MCP-1 production.
These findings indicate that PARS inhibition in the AM blunts their response to oxidative stress and may help explain the protective effects of intratracheal PARS inhibition in LIRI. |
| doi_str_mv | 10.1016/j.yexmp.2007.11.005 |
| format | Article |
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in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to characterize the effects of PARS on AM activation in response to oxidative stress.
Primary cultures of AM were rendered hypoxic for 2 h and reoxygenated for up to 4 h. Cells were preincubated with INO-1001, a specific PARS inhibitor 1 h prior to hypoxia. Gel shift assays characterized nuclear factor kappa B (NFκB), and enzyme linked immunosorbent assay quantitated chemokine/cytokine protein secretion.
Hypoxia and reoxygenation resulted in an increase in the early nuclear translocation of NFκB, and an increase in the secretion of the cytokine tumor necrosis factor-alpha (TNF-α), chemokines macrophage inflammatory protein (MIP-1α), monocyte chemoattractant protein one (MCP-1) and cytokine induced neutrophil chemoattractant (CINC). Pretreatment of AM with INO-1001 decreased both the early translocation of NFκB and the production of TNF-α (
p
<
0.05) and MIP-1α
p
=
0.02, but did not affect CINC or MCP-1 production.
These findings indicate that PARS inhibition in the AM blunts their response to oxidative stress and may help explain the protective effects of intratracheal PARS inhibition in LIRI.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2007.11.005</identifier><identifier>PMID: 18206870</identifier><identifier>CODEN: EXMPA6</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Alveolar macrophage ; Animals ; Biological and medical sciences ; Cardiology. Vascular system ; Cell Survival - drug effects ; Cells, Cultured ; Chemokines ; Chemokines - metabolism ; Enzyme Inhibitors - pharmacology ; Hypoxia ; Hypoxia - enzymology ; In vitro ; Indoles - pharmacology ; Investigative techniques, diagnostic techniques (general aspects) ; Lung ischemia reperfusion injury cytokines ; Macrophages, Alveolar - enzymology ; Male ; Medical sciences ; NF-kappa B - metabolism ; Oxidative Stress - drug effects ; Oxygen - metabolism ; PARS ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases - metabolism ; Rats ; Rats, Long-Evans ; Reoxygenation ; Specific Pathogen-Free Organisms</subject><ispartof>Experimental and molecular pathology, 2008-04, Vol.84 (2), p.141-144</ispartof><rights>2007</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-720260e6316c13512cea53d84709a820e51348f5c3b829e8798e1a00aead87cd3</citedby><cites>FETCH-LOGICAL-c387t-720260e6316c13512cea53d84709a820e51348f5c3b829e8798e1a00aead87cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S001448000700144X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20264428$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18206870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCourtie, Anton S.</creatorcontrib><creatorcontrib>Farivar, Alexander S.</creatorcontrib><creatorcontrib>Woolley, Steven M.</creatorcontrib><creatorcontrib>Merry, Heather E.</creatorcontrib><creatorcontrib>Wolf, Patrick S.</creatorcontrib><creatorcontrib>Szabo, Csaba</creatorcontrib><creatorcontrib>Mulligan, Michael S.</creatorcontrib><title>Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation</title><title>Experimental and molecular pathology</title><addtitle>Exp Mol Pathol</addtitle><description>Inhibition of the nuclear enzyme poly ribose synthetase (PARS) protects against
in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to characterize the effects of PARS on AM activation in response to oxidative stress.
Primary cultures of AM were rendered hypoxic for 2 h and reoxygenated for up to 4 h. Cells were preincubated with INO-1001, a specific PARS inhibitor 1 h prior to hypoxia. Gel shift assays characterized nuclear factor kappa B (NFκB), and enzyme linked immunosorbent assay quantitated chemokine/cytokine protein secretion.
Hypoxia and reoxygenation resulted in an increase in the early nuclear translocation of NFκB, and an increase in the secretion of the cytokine tumor necrosis factor-alpha (TNF-α), chemokines macrophage inflammatory protein (MIP-1α), monocyte chemoattractant protein one (MCP-1) and cytokine induced neutrophil chemoattractant (CINC). Pretreatment of AM with INO-1001 decreased both the early translocation of NFκB and the production of TNF-α (
p
<
0.05) and MIP-1α
p
=
0.02, but did not affect CINC or MCP-1 production.
These findings indicate that PARS inhibition in the AM blunts their response to oxidative stress and may help explain the protective effects of intratracheal PARS inhibition in LIRI.</description><subject>Alveolar macrophage</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Chemokines</subject><subject>Chemokines - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Hypoxia</subject><subject>Hypoxia - enzymology</subject><subject>In vitro</subject><subject>Indoles - pharmacology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lung ischemia reperfusion injury cytokines</subject><subject>Macrophages, Alveolar - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>NF-kappa B - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen - metabolism</subject><subject>PARS</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Reoxygenation</subject><subject>Specific Pathogen-Free Organisms</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi0EokvhFyAhX0BwSBjn0zlwqAqUSpXoAc7WrD2761ViBztbbf59HXYFt0qWZg7PO555GHsrIBcgms_7fKbjMOYFQJsLkQPUz9hKQNdk0FX1c7YCEFVWSYAL9irGPQB0IIqX7ELIAhrZwoqZe9_P_OPV1_tPPNi1j8Tj7KYdTZha63Z2bSfrXWo59g_kewx8QB38uMMtRX5whsLWW7flu3n0R4scneGB_HHeksMl_Jq92GAf6c25XrLf37_9uv6R3f28ub2-ust0KdspawsoGqCmFI0WZS0KTViXRlYtdJg2plqUldzUulzLoiPZdpIEAiChka025SX7cJo7Bv_nQHFSg42a-h4d-UNULVRVejKB5QlMd8QYaKPGYAcMsxKgFrlqr_7KVYtcJYRKclPq3Xn8YT2Q-Z8520zA-zOAUWO_Cei0jf-45byqKpbvv5w4SjIeLAUVtSWnydhAelLG2ycXeQSOt5mV</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>McCourtie, Anton S.</creator><creator>Farivar, Alexander S.</creator><creator>Woolley, Steven M.</creator><creator>Merry, Heather E.</creator><creator>Wolf, Patrick S.</creator><creator>Szabo, Csaba</creator><creator>Mulligan, Michael S.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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></search><sort><creationdate>20080401</creationdate><title>Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation</title><author>McCourtie, Anton S. ; Farivar, Alexander S. ; Woolley, Steven M. ; Merry, Heather E. ; Wolf, Patrick S. ; Szabo, Csaba ; Mulligan, Michael S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-720260e6316c13512cea53d84709a820e51348f5c3b829e8798e1a00aead87cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Alveolar macrophage</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Chemokines</topic><topic>Chemokines - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Hypoxia</topic><topic>Hypoxia - enzymology</topic><topic>In vitro</topic><topic>Indoles - pharmacology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Lung ischemia reperfusion injury cytokines</topic><topic>Macrophages, Alveolar - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxygen - metabolism</topic><topic>PARS</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Reoxygenation</topic><topic>Specific Pathogen-Free Organisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCourtie, Anton S.</creatorcontrib><creatorcontrib>Farivar, Alexander S.</creatorcontrib><creatorcontrib>Woolley, Steven M.</creatorcontrib><creatorcontrib>Merry, Heather E.</creatorcontrib><creatorcontrib>Wolf, Patrick S.</creatorcontrib><creatorcontrib>Szabo, Csaba</creatorcontrib><creatorcontrib>Mulligan, Michael S.</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCourtie, Anton S.</au><au>Farivar, Alexander S.</au><au>Woolley, Steven M.</au><au>Merry, Heather E.</au><au>Wolf, Patrick S.</au><au>Szabo, Csaba</au><au>Mulligan, Michael S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>84</volume><issue>2</issue><spage>141</spage><epage>144</epage><pages>141-144</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><coden>EXMPA6</coden><abstract>Inhibition of the nuclear enzyme poly ribose synthetase (PARS) protects against
in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to characterize the effects of PARS on AM activation in response to oxidative stress.
Primary cultures of AM were rendered hypoxic for 2 h and reoxygenated for up to 4 h. Cells were preincubated with INO-1001, a specific PARS inhibitor 1 h prior to hypoxia. Gel shift assays characterized nuclear factor kappa B (NFκB), and enzyme linked immunosorbent assay quantitated chemokine/cytokine protein secretion.
Hypoxia and reoxygenation resulted in an increase in the early nuclear translocation of NFκB, and an increase in the secretion of the cytokine tumor necrosis factor-alpha (TNF-α), chemokines macrophage inflammatory protein (MIP-1α), monocyte chemoattractant protein one (MCP-1) and cytokine induced neutrophil chemoattractant (CINC). Pretreatment of AM with INO-1001 decreased both the early translocation of NFκB and the production of TNF-α (
p
<
0.05) and MIP-1α
p
=
0.02, but did not affect CINC or MCP-1 production.
These findings indicate that PARS inhibition in the AM blunts their response to oxidative stress and may help explain the protective effects of intratracheal PARS inhibition in LIRI.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>18206870</pmid><doi>10.1016/j.yexmp.2007.11.005</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alveolar macrophage Animals Biological and medical sciences Cardiology. Vascular system Cell Survival - drug effects Cells, Cultured Chemokines Chemokines - metabolism Enzyme Inhibitors - pharmacology Hypoxia Hypoxia - enzymology In vitro Indoles - pharmacology Investigative techniques, diagnostic techniques (general aspects) Lung ischemia reperfusion injury cytokines Macrophages, Alveolar - enzymology Male Medical sciences NF-kappa B - metabolism Oxidative Stress - drug effects Oxygen - metabolism PARS Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases - metabolism Rats Rats, Long-Evans Reoxygenation Specific Pathogen-Free Organisms |
| title | Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation |
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