Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products
Conformational alterations of bovine hemoglobin (Hb) upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary...
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| description | Conformational alterations of bovine hemoglobin (Hb) upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD) and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT) fluorescence and red shifted Congo Red (CR) absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs) were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's. |
| doi_str_mv | 10.1371/journal.pone.0072075 |
| format | Article |
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At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD) and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT) fluorescence and red shifted Congo Red (CR) absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs) were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0072075</identifier><identifier>PMID: 23991043</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Absorbance ; Advanced glycosylation end products ; Age ; Aggregates ; Amyloidogenesis ; Animals ; Binding ; Bioassay ; Bioassays ; Biochemistry ; Biology ; Cattle ; Chromatography ; Circular Dichroism ; Comet assay ; Congo Red - chemistry ; Damage detection ; Diabetes ; Diabetes mellitus ; Dichroism ; Dimers ; Doppler effect ; Electron microscopy ; Fibrils ; Fluorescence ; Genetic transformation ; Genotoxicity ; Glycation End Products, Advanced - chemistry ; Glycosylation ; Glyoxal - chemistry ; Heme ; Hemoglobin ; Hemoglobins - chemistry ; Interdisciplinary aspects ; Life sciences ; Ligands ; Medicine ; Microscopy, Electron, Scanning ; Protein Conformation ; Protein structure ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins ; Red shift ; Scanning electron microscopy ; Secondary structure ; Size exclusion chromatography ; Sodium ; Spectrometry, Fluorescence ; Spectroscopy, Fourier Transform Infrared ; Studies ; Tertiary structure ; Thiazoles - chemistry ; Time Factors ; Toxicity ; Transformation ; Tryptophan ; Tryptophan - chemistry</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e72075-e72075</ispartof><rights>2013 Iram et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD) and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT) fluorescence and red shifted Congo Red (CR) absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs) were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.</description><subject>Absorbance</subject><subject>Advanced glycosylation end products</subject><subject>Age</subject><subject>Aggregates</subject><subject>Amyloidogenesis</subject><subject>Animals</subject><subject>Binding</subject><subject>Bioassay</subject><subject>Bioassays</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Cattle</subject><subject>Chromatography</subject><subject>Circular Dichroism</subject><subject>Comet assay</subject><subject>Congo Red - chemistry</subject><subject>Damage detection</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Dichroism</subject><subject>Dimers</subject><subject>Doppler effect</subject><subject>Electron microscopy</subject><subject>Fibrils</subject><subject>Fluorescence</subject><subject>Genetic transformation</subject><subject>Genotoxicity</subject><subject>Glycation End Products, Advanced - chemistry</subject><subject>Glycosylation</subject><subject>Glyoxal - chemistry</subject><subject>Heme</subject><subject>Hemoglobin</subject><subject>Hemoglobins - chemistry</subject><subject>Interdisciplinary aspects</subject><subject>Life sciences</subject><subject>Ligands</subject><subject>Medicine</subject><subject>Microscopy, Electron, Scanning</subject><subject>Protein Conformation</subject><subject>Protein structure</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Red shift</subject><subject>Scanning electron microscopy</subject><subject>Secondary structure</subject><subject>Size exclusion chromatography</subject><subject>Sodium</subject><subject>Spectrometry, Fluorescence</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>Studies</subject><subject>Tertiary structure</subject><subject>Thiazoles - chemistry</subject><subject>Time Factors</subject><subject>Toxicity</subject><subject>Transformation</subject><subject>Tryptophan</subject><subject>Tryptophan - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iram, Afshin</au><au>Alam, Tauqeer</au><au>Khan, Javed M</au><au>Khan, Taqi A</au><au>Khan, Rizwan H</au><au>Naeem, Aabgeena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-26</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e72075</spage><epage>e72075</epage><pages>e72075-e72075</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Conformational alterations of bovine hemoglobin (Hb) upon sequential addition of glyoxal over a range of 0-90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD) and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT) fluorescence and red shifted Congo Red (CR) absorbance. On incubating Hb with 30% v/v glyoxal for 0-20 days, advanced glycation end products (AGEs) were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington's.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23991043</pmid><doi>10.1371/journal.pone.0072075</doi><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| subjects | Absorbance Advanced glycosylation end products Age Aggregates Amyloidogenesis Animals Binding Bioassay Bioassays Biochemistry Biology Cattle Chromatography Circular Dichroism Comet assay Congo Red - chemistry Damage detection Diabetes Diabetes mellitus Dichroism Dimers Doppler effect Electron microscopy Fibrils Fluorescence Genetic transformation Genotoxicity Glycation End Products, Advanced - chemistry Glycosylation Glyoxal - chemistry Heme Hemoglobin Hemoglobins - chemistry Interdisciplinary aspects Life sciences Ligands Medicine Microscopy, Electron, Scanning Protein Conformation Protein structure Protein Structure, Secondary Protein Structure, Tertiary Proteins Red shift Scanning electron microscopy Secondary structure Size exclusion chromatography Sodium Spectrometry, Fluorescence Spectroscopy, Fourier Transform Infrared Studies Tertiary structure Thiazoles - chemistry Time Factors Toxicity Transformation Tryptophan Tryptophan - chemistry |
| title | Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T03%3A24%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Molten%20globule%20of%20hemoglobin%20proceeds%20into%20aggregates%20and%20advanced%20glycated%20end%20products&rft.jtitle=PloS%20one&rft.au=Iram,%20Afshin&rft.date=2013-08-26&rft.volume=8&rft.issue=8&rft.spage=e72075&rft.epage=e72075&rft.pages=e72075-e72075&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0072075&rft_dat=%3Cproquest_plos_%3E1429215282%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428060352&rft_id=info:pmid/23991043&rft_doaj_id=oai_doaj_org_article_2257fdce766045d894e410650fa81ce1&rfr_iscdi=true |