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...
Gespeichert in:
Veröffentlicht in: | Archives of biochemistry and biophysics 1993-06, Vol.303 (2), p.332-338 |
---|---|
Hauptverfasser: | , , , , |
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 & 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>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4779184$$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 & 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 & 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 |