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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Oxidative Stress Effect
of Dopamine on α-Synuclein:
Electroanalysis of Solvent Interactions</title>
<author><name sortKey="Chan, Tiffiny" sort="Chan, Tiffiny" uniqKey="Chan T" first="Tiffiny" last="Chan">Tiffiny Chan</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chow, Ari M" sort="Chow, Ari M" uniqKey="Chow A" first="Ari M." last="Chow">Ari M. Chow</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cheng, Xin R" sort="Cheng, Xin R" uniqKey="Cheng X" first="Xin R." last="Cheng">Xin R. Cheng</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tang, Derek X0a W F" sort="Tang, Derek X0a W F" uniqKey="Tang D" first="Derek X0a W. F." last="Tang">Derek X0a W. F. Tang</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Ian R" sort="Brown, Ian R" uniqKey="Brown I" first="Ian R." last="Brown">Ian R. Brown</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kerman, Kagan" sort="Kerman, Kagan" uniqKey="Kerman K" first="Kagan" last="Kerman">Kagan Kerman</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22860226</idno>
<idno type="pmc">3399574</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399574</idno>
<idno type="RBID">PMC:3399574</idno>
<idno type="doi">10.1021/cn300034t</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000187</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000187</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Oxidative Stress Effect
of Dopamine on α-Synuclein:
Electroanalysis of Solvent Interactions</title>
<author><name sortKey="Chan, Tiffiny" sort="Chan, Tiffiny" uniqKey="Chan T" first="Tiffiny" last="Chan">Tiffiny Chan</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chow, Ari M" sort="Chow, Ari M" uniqKey="Chow A" first="Ari M." last="Chow">Ari M. Chow</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cheng, Xin R" sort="Cheng, Xin R" uniqKey="Cheng X" first="Xin R." last="Cheng">Xin R. Cheng</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tang, Derek X0a W F" sort="Tang, Derek X0a W F" uniqKey="Tang D" first="Derek X0a W. F." last="Tang">Derek X0a W. F. Tang</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Ian R" sort="Brown, Ian R" uniqKey="Brown I" first="Ian R." last="Brown">Ian R. Brown</name>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kerman, Kagan" sort="Kerman, Kagan" uniqKey="Kerman K" first="Kagan" last="Kerman">Kagan Kerman</name>
<affiliation><nlm:aff id="aff1">Department of Physical and Environmental Sciences,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1">Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">ACS Chemical Neuroscience</title>
<idno type="ISSN">1948-7193</idno>
<idno type="eISSN">1948-7193</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="cn-2012-00034t_0003" id="ab-tgr1"></graphic>
</p>
<p>The interaction of dopamine (DA) and α-synuclein
(α-S)
can lead to protein misfolding and neuronal death triggered by oxidative
stress relevant to the progression of Parkinson’s disease (PD).
In this study, interfacial properties associated with DA-induced α-S
aggregation under various solution conditions (i.e., pH, ionic strength)
were investigated in vitro. The electrochemical oxidation of tyrosine
(Tyr) residues in α-S was detected in the presence of DA. DA
concentration dependence was analyzed and found to significantly affect
α-S aggregation pathways. At low pH, DA was shown to be stable
and produced no observable difference in interfacial properties. Between
pH 7 and 11, DA promoted α-S aggregation. Significant differences
in oxidation current signals in response to high pH and ionic strength
suggested the importance of initial interactions in the stabilization
of toxic oligomeric structures and subsequent off-pathways of α-S.
Our results demonstrate the importance of solution interactions with
α-S and the unique information that electrochemical techniques
can provide for the investigation of α-S aggregation at early
stages, an important step toward the development of future PD therapeutics.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ACS Chem Neurosci</journal-id>
<journal-id journal-id-type="iso-abbrev">ACS Chem Neurosci</journal-id>
<journal-id journal-id-type="publisher-id">cn</journal-id>
<journal-id journal-id-type="coden">acncdm</journal-id>
<journal-title-group><journal-title>ACS Chemical Neuroscience</journal-title>
</journal-title-group>
<issn pub-type="ppub">1948-7193</issn>
<issn pub-type="epub">1948-7193</issn>
<publisher><publisher-name>American Chemical
Society</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22860226</article-id>
<article-id pub-id-type="pmc">3399574</article-id>
<article-id pub-id-type="doi">10.1021/cn300034t</article-id>
<article-categories><subj-group><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Oxidative Stress Effect
of Dopamine on α-Synuclein:
Electroanalysis of Solvent Interactions</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Chan</surname>
<given-names>Tiffiny</given-names>
</name>
<xref rid="aff1" ref-type="aff">†</xref>
</contrib>
<contrib contrib-type="author" id="ath2"><name><surname>Chow</surname>
<given-names>Ari M.</given-names>
</name>
<xref rid="aff1" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" id="ath3"><name><surname>Cheng</surname>
<given-names>Xin R.</given-names>
</name>
<xref rid="aff1" ref-type="aff">†</xref>
</contrib>
<contrib contrib-type="author" id="ath4"><name><surname>Tang</surname>
<given-names>Derek
W. F.</given-names>
</name>
<xref rid="aff1" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" id="ath5"><name><surname>Brown</surname>
<given-names>Ian R.</given-names>
</name>
<xref rid="aff1" ref-type="aff">‡</xref>
</contrib>
<contrib contrib-type="author" corresp="yes" id="ath6"><name><surname>Kerman</surname>
<given-names>Kagan</given-names>
</name>
<xref rid="cor1" ref-type="other">*</xref>
<xref rid="aff1" ref-type="aff">†</xref>
<xref rid="aff1" ref-type="aff">‡</xref>
</contrib>
<aff id="aff1"><sup>†</sup>
Department of Physical and Environmental Sciences,<sup>‡</sup>
Centre for the Neurobiology of Stress, Department of Biological Sciences,<institution>University of Toronto Scarborough</institution>
, 1265 Military Trail, Toronto, ON, M1C 1A4 Canada</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
E-mail: <email>kagan.kerman@utoronto.ca</email>
. Telephone: <phone>+1-416-287-7249</phone>
.</corresp>
</author-notes>
<pub-date pub-type="epub"><day>16</day>
<month>05</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="collection"><day>18</day>
<month>07</month>
<year>2012</year>
</pub-date>
<volume>3</volume>
<issue>7</issue>
<fpage>569</fpage>
<lpage>574</lpage>
<history><date date-type="received"><day>14</day>
<month>03</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>16</day>
<month>05</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012 American Chemical Society</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>American Chemical Society</copyright-holder>
</permissions>
<abstract><p content-type="toc-graphic"><graphic xlink:href="cn-2012-00034t_0003" id="ab-tgr1"></graphic>
</p>
<p>The interaction of dopamine (DA) and α-synuclein
(α-S)
can lead to protein misfolding and neuronal death triggered by oxidative
stress relevant to the progression of Parkinson’s disease (PD).
In this study, interfacial properties associated with DA-induced α-S
aggregation under various solution conditions (i.e., pH, ionic strength)
were investigated in vitro. The electrochemical oxidation of tyrosine
(Tyr) residues in α-S was detected in the presence of DA. DA
concentration dependence was analyzed and found to significantly affect
α-S aggregation pathways. At low pH, DA was shown to be stable
and produced no observable difference in interfacial properties. Between
pH 7 and 11, DA promoted α-S aggregation. Significant differences
in oxidation current signals in response to high pH and ionic strength
suggested the importance of initial interactions in the stabilization
of toxic oligomeric structures and subsequent off-pathways of α-S.
Our results demonstrate the importance of solution interactions with
α-S and the unique information that electrochemical techniques
can provide for the investigation of α-S aggregation at early
stages, an important step toward the development of future PD therapeutics.</p>
</abstract>
<kwd-group><kwd>Dopamine</kwd>
<kwd>electroanalysis</kwd>
<kwd>α-synuclein</kwd>
<kwd>aggregation</kwd>
<kwd>tyrosine</kwd>
<kwd>Parkinson’s disease</kwd>
</kwd-group>
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<meta-value>cn300034t</meta-value>
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<custom-meta><meta-name>document-id-new-14</meta-name>
<meta-value>cn-2012-00034t</meta-value>
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<notes id="notes-500"><title>Author Contributions</title>
<p>T.C., A.M.C.,
X.R.C., and D.W.F.T. designed and performed experiments, analysed
data, and wrote the paper; I.R.B. and K.K. provided biological and
analytical tools, designed experiments, analysed data, and wrote the
paper.</p>
</notes>
</front>
</pmc>
</record>
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