Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits

We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as t...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Archives of biochemistry and biophysics 1993-06, Vol.303 (2), p.332-338
Hauptverfasser: Alayash, A.I., Fratantoni, J.C., Bonaventura, C., Bonaventura, J., Cashon, R.E.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 338
container_issue 2
container_start_page 332
container_title Archives of biochemistry and biophysics
container_volume 303
creator Alayash, A.I.
Fratantoni, J.C.
Bonaventura, C.
Bonaventura, J.
Cashon, R.E.
description We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the α chains with bis(3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the β chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of α and β chains. The structural modifications result in altered rate constants for NO binding to both α and β chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity.
doi_str_mv 10.1006/abbi.1993.1292
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_75772321</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0003986183712920</els_id><sourcerecordid>75772321</sourcerecordid><originalsourceid>FETCH-LOGICAL-c283t-dbcfb82da10090c3104306b4b1c8060083c7786b7dcbecc6634736967e294cfe3</originalsourceid><addsrcrecordid>eNp1kLtu1UAQhlcIFA6Blg5pC0Tnw16cvZRwlBCkI1IAHdJqL-NkwF6HXTvAY8GD8EzYOkfpaGaK-WY0_0fIc862nDH12oeAW26t3HJhxQOy4cyqhknTPiQbxphsrFH8MXlS61fGOG-VOCEn5owLye2GfPmAU8FIr35iAvoWc8J8TaeRXs6Dz_QCSsEbGMbrfgyYK92VsdZmj_kbJBpg-gGQ6TlON1Do3990XOof-nEOc8apPiWPOt9XeHbsp-Tzxfmn3WWzv3r3fvdm30Rh5NSkELtgRPJLIMui5KyVTIU28GiYYszIqLVRQacYIEalZKulskqDsG3sQJ6SV4e7t2X8PkOd3IA1Qt_7DONcnT7TWkjBF3B7AOMao0DnbgsOvvxynLlVp1t1ulWnW3UuCy-Ol-cwQLrHj_6W-cvj3Nfo-674HLHeY63Wlpt2wcwBg8XCHUJxNSLkCAkLxMmlEf_3wT-n_ZF5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>75772321</pqid></control><display><type>article</type><title>Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits</title><source>Elsevier ScienceDirect Journals Complete - AutoHoldings</source><source>MEDLINE</source><creator>Alayash, A.I. ; Fratantoni, J.C. ; Bonaventura, C. ; Bonaventura, J. ; Cashon, R.E.</creator><creatorcontrib>Alayash, A.I. ; Fratantoni, J.C. ; Bonaventura, C. ; Bonaventura, J. ; Cashon, R.E.</creatorcontrib><description>We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the α chains with bis(3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the β chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of α and β chains. The structural modifications result in altered rate constants for NO binding to both α and β chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity.</description><identifier>ISSN: 0003-9861</identifier><identifier>EISSN: 1096-0384</identifier><identifier>DOI: 10.1006/abbi.1993.1292</identifier><identifier>PMID: 8512319</identifier><identifier>CODEN: ABBIA4</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Analytical, structural and metabolic biochemistry ; Aspirin - analogs &amp; derivatives ; Biological and medical sciences ; Cross-Linking Reagents ; Drug Stability ; Fundamental and applied biological sciences. Psychology ; Hemoproteins ; Humans ; Kinetics ; Macromolecular Substances ; Metalloproteins ; Methemoglobin - metabolism ; Nitric Oxide - metabolism ; Oxidation-Reduction ; Oxygen - metabolism ; Proteins ; Spectrophotometry</subject><ispartof>Archives of biochemistry and biophysics, 1993-06, Vol.303 (2), p.332-338</ispartof><rights>1993 Academic Press</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c283t-dbcfb82da10090c3104306b4b1c8060083c7786b7dcbecc6634736967e294cfe3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/abbi.1993.1292$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=4779184$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8512319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alayash, A.I.</creatorcontrib><creatorcontrib>Fratantoni, J.C.</creatorcontrib><creatorcontrib>Bonaventura, C.</creatorcontrib><creatorcontrib>Bonaventura, J.</creatorcontrib><creatorcontrib>Cashon, R.E.</creatorcontrib><title>Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits</title><title>Archives of biochemistry and biophysics</title><addtitle>Arch Biochem Biophys</addtitle><description>We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the α chains with bis(3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the β chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of α and β chains. The structural modifications result in altered rate constants for NO binding to both α and β chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Aspirin - analogs &amp; derivatives</subject><subject>Biological and medical sciences</subject><subject>Cross-Linking Reagents</subject><subject>Drug Stability</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemoproteins</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Macromolecular Substances</subject><subject>Metalloproteins</subject><subject>Methemoglobin - metabolism</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Oxygen - metabolism</subject><subject>Proteins</subject><subject>Spectrophotometry</subject><issn>0003-9861</issn><issn>1096-0384</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtu1UAQhlcIFA6Blg5pC0Tnw16cvZRwlBCkI1IAHdJqL-NkwF6HXTvAY8GD8EzYOkfpaGaK-WY0_0fIc862nDH12oeAW26t3HJhxQOy4cyqhknTPiQbxphsrFH8MXlS61fGOG-VOCEn5owLye2GfPmAU8FIr35iAvoWc8J8TaeRXs6Dz_QCSsEbGMbrfgyYK92VsdZmj_kbJBpg-gGQ6TlON1Do3990XOof-nEOc8apPiWPOt9XeHbsp-Tzxfmn3WWzv3r3fvdm30Rh5NSkELtgRPJLIMui5KyVTIU28GiYYszIqLVRQacYIEalZKulskqDsG3sQJ6SV4e7t2X8PkOd3IA1Qt_7DONcnT7TWkjBF3B7AOMao0DnbgsOvvxynLlVp1t1ulWnW3UuCy-Ol-cwQLrHj_6W-cvj3Nfo-674HLHeY63Wlpt2wcwBg8XCHUJxNSLkCAkLxMmlEf_3wT-n_ZF5</recordid><startdate>199306</startdate><enddate>199306</enddate><creator>Alayash, A.I.</creator><creator>Fratantoni, J.C.</creator><creator>Bonaventura, C.</creator><creator>Bonaventura, J.</creator><creator>Cashon, R.E.</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>199306</creationdate><title>Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits</title><author>Alayash, A.I. ; Fratantoni, J.C. ; Bonaventura, C. ; Bonaventura, J. ; Cashon, R.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c283t-dbcfb82da10090c3104306b4b1c8060083c7786b7dcbecc6634736967e294cfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Aspirin - analogs &amp; derivatives</topic><topic>Biological and medical sciences</topic><topic>Cross-Linking Reagents</topic><topic>Drug Stability</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hemoproteins</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Macromolecular Substances</topic><topic>Metalloproteins</topic><topic>Methemoglobin - metabolism</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Oxygen - metabolism</topic><topic>Proteins</topic><topic>Spectrophotometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alayash, A.I.</creatorcontrib><creatorcontrib>Fratantoni, J.C.</creatorcontrib><creatorcontrib>Bonaventura, C.</creatorcontrib><creatorcontrib>Bonaventura, J.</creatorcontrib><creatorcontrib>Cashon, R.E.</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>Archives of biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alayash, A.I.</au><au>Fratantoni, J.C.</au><au>Bonaventura, C.</au><au>Bonaventura, J.</au><au>Cashon, R.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits</atitle><jtitle>Archives of biochemistry and biophysics</jtitle><addtitle>Arch Biochem Biophys</addtitle><date>1993-06</date><risdate>1993</risdate><volume>303</volume><issue>2</issue><spage>332</spage><epage>338</epage><pages>332-338</pages><issn>0003-9861</issn><eissn>1096-0384</eissn><coden>ABBIA4</coden><abstract>We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the α chains with bis(3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the β chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of α and β chains. The structural modifications result in altered rate constants for NO binding to both α and β chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>8512319</pmid><doi>10.1006/abbi.1993.1292</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0003-9861
ispartof Archives of biochemistry and biophysics, 1993-06, Vol.303 (2), p.332-338
issn 0003-9861
1096-0384
language eng
recordid cdi_proquest_miscellaneous_75772321
source Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE
subjects Analytical, structural and metabolic biochemistry
Aspirin - analogs & derivatives
Biological and medical sciences
Cross-Linking Reagents
Drug Stability
Fundamental and applied biological sciences. Psychology
Hemoproteins
Humans
Kinetics
Macromolecular Substances
Metalloproteins
Methemoglobin - metabolism
Nitric Oxide - metabolism
Oxidation-Reduction
Oxygen - metabolism
Proteins
Spectrophotometry
title Nitric Oxide Binding to Human Ferrihemoglobins Cross-Linked between Either α or β Subunits
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T09%3A01%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nitric%20Oxide%20Binding%20to%20Human%20Ferrihemoglobins%20Cross-Linked%20between%20Either%20%CE%B1%20or%20%CE%B2%20Subunits&rft.jtitle=Archives%20of%20biochemistry%20and%20biophysics&rft.au=Alayash,%20A.I.&rft.date=1993-06&rft.volume=303&rft.issue=2&rft.spage=332&rft.epage=338&rft.pages=332-338&rft.issn=0003-9861&rft.eissn=1096-0384&rft.coden=ABBIA4&rft_id=info:doi/10.1006/abbi.1993.1292&rft_dat=%3Cproquest_cross%3E75772321%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=75772321&rft_id=info:pmid/8512319&rft_els_id=S0003986183712920&rfr_iscdi=true