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Evidence of Increased Oxidative Stress in Aged Mesenteric Lymphatic Vessels

Identifieur interne : 004D16 ( Ncbi/Merge ); précédent : 004D15; suivant : 004D17

Evidence of Increased Oxidative Stress in Aged Mesenteric Lymphatic Vessels

Auteurs : Sangeetha Thangaswamy ; Eric A. Bridenbaugh ; Anatoliy A. Gashev

Source :

RBID : PMC:3378181

Abstract

AbstractBackground

We have previously shown that aging is associated with weakened rat mesenteric lymphatic vessel (MLV) contractility. However, the specific mechanisms contributing to this aging-associated contractile degeneration remain unknown. Aging is often associated with elevations in oxidative stress, and reactive oxygen species (ROS) have been shown to reduce the contractility of MLV. Thus in the present study, we sought to assess whether aging is associated with increased levels of oxidative stress and oxidative damage in MLV.

Methods and Results

MLV were isolated from 9-mo- and 24-mo-old Fischer-344 rats and subjected to the following experimental techniques: measurement of total superoxide dismutase (SOD) activity; estimation of lipid peroxidation levels via measurement of thiobarbituric acid reactive substances (TBARS); detection of superoxide and mitochondrial ROS in live MLV; Western blot analysis, and immunohistochemical labeling of the SOD isoforms and nitro-tyrosine proteins. We found that aging is associated with increased levels of cellular superoxide and mitochondrial ROS concomitant with a reduction in Cu/Zn-SOD protein expression and total SOD enzymatic activity in MLV. This increase in oxidative stress and decrease in antioxidant activity was associated with evidence of increased lipid (as indicated by TBARS) and protein (as indicated by nitro-tyrosine labeling) oxidative damage.

Conclusions

Thus for the first time, we demonstrate that aging-associated increases in oxidative stress and oxidative damage is indeed present in the walls of MLV and may contribute to the aging-associated lymphatic pump dysfunction we previously reported.


Url:
DOI: 10.1089/lrb.2011.0022
PubMed: 22540739
PubMed Central: 3378181

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PMC:3378181

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<name sortKey="Thangaswamy, Sangeetha" sort="Thangaswamy, Sangeetha" uniqKey="Thangaswamy S" first="Sangeetha" last="Thangaswamy">Sangeetha Thangaswamy</name>
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<name sortKey="Bridenbaugh, Eric A" sort="Bridenbaugh, Eric A" uniqKey="Bridenbaugh E" first="Eric A." last="Bridenbaugh">Eric A. Bridenbaugh</name>
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<name sortKey="Gashev, Anatoliy A" sort="Gashev, Anatoliy A" uniqKey="Gashev A" first="Anatoliy A." last="Gashev">Anatoliy A. Gashev</name>
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<title>Background</title>
<p>We have previously shown that aging is associated with weakened rat mesenteric lymphatic vessel (MLV) contractility. However, the specific mechanisms contributing to this aging-associated contractile degeneration remain unknown. Aging is often associated with elevations in oxidative stress, and reactive oxygen species (ROS) have been shown to reduce the contractility of MLV. Thus in the present study, we sought to assess whether aging is associated with increased levels of oxidative stress and oxidative damage in MLV.</p>
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<sec>
<title>Methods and Results</title>
<p>MLV were isolated from 9-mo- and 24-mo-old Fischer-344 rats and subjected to the following experimental techniques: measurement of total superoxide dismutase (SOD) activity; estimation of lipid peroxidation levels via measurement of thiobarbituric acid reactive substances (TBARS); detection of superoxide and mitochondrial ROS in live MLV; Western blot analysis, and immunohistochemical labeling of the SOD isoforms and nitro-tyrosine proteins. We found that aging is associated with increased levels of cellular superoxide and mitochondrial ROS concomitant with a reduction in Cu/Zn-SOD protein expression and total SOD enzymatic activity in MLV. This increase in oxidative stress and decrease in antioxidant activity was associated with evidence of increased lipid (as indicated by TBARS) and protein (as indicated by nitro-tyrosine labeling) oxidative damage.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>Thus for the first time, we demonstrate that aging-associated increases in oxidative stress and oxidative damage is indeed present in the walls of MLV and may contribute to the aging-associated lymphatic pump dysfunction we previously reported.</p>
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<journal-id journal-id-type="nlm-ta">Lymphat Res Biol</journal-id>
<journal-id journal-id-type="iso-abbrev">Lymphat Res Biol</journal-id>
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<publisher-loc>140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA</publisher-loc>
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<surname>Thangaswamy</surname>
<given-names>Sangeetha</given-names>
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<name>
<surname>Bridenbaugh</surname>
<given-names>Eric A.</given-names>
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<degrees>Ph.D.</degrees>
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<given-names>Anatoliy A.</given-names>
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<degrees>M.D., Ph.D., D. Med. Sci.</degrees>
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<aff id="aff1">Department of Systems Biology and Translational Medicine, College of Medicine,
<institution>Texas A&M Health Science Center</institution>
, Temple, Texas.</aff>
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<p>This work was supported in parts by the National Institutes of Health (NIH RO1 AG-030578 and HL-094269) and by Texas A&M Health Science Center College of Medicine and Department of Systems Biology and Translational Medicine.</p>
</fn>
<corresp>Address correspondence to:
<italic>Anatoliy A. Gashev, M.D., Ph.D., D. Med. Sci., Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, 702 SW H.K. Dodgen Loop, Temple, TX 76504, E-mail</italic>
:
<email xlink:href="mailto:gashev@tamu.edu">gashev@tamu.edu</email>
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<month>6</month>
<year>2012</year>
<pmc-comment>string-date: June 2012</pmc-comment>
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<volume>10</volume>
<issue>2</issue>
<fpage>53</fpage>
<lpage>62</lpage>
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<copyright-statement>Copyright 2012, Mary Ann Liebert, Inc.</copyright-statement>
<copyright-year>2012</copyright-year>
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<self-uri xlink:type="simple" xlink:href="lrb.2011.0022.pdf"></self-uri>
<abstract>
<title>Abstract</title>
<sec>
<title>Background</title>
<p>We have previously shown that aging is associated with weakened rat mesenteric lymphatic vessel (MLV) contractility. However, the specific mechanisms contributing to this aging-associated contractile degeneration remain unknown. Aging is often associated with elevations in oxidative stress, and reactive oxygen species (ROS) have been shown to reduce the contractility of MLV. Thus in the present study, we sought to assess whether aging is associated with increased levels of oxidative stress and oxidative damage in MLV.</p>
</sec>
<sec>
<title>Methods and Results</title>
<p>MLV were isolated from 9-mo- and 24-mo-old Fischer-344 rats and subjected to the following experimental techniques: measurement of total superoxide dismutase (SOD) activity; estimation of lipid peroxidation levels via measurement of thiobarbituric acid reactive substances (TBARS); detection of superoxide and mitochondrial ROS in live MLV; Western blot analysis, and immunohistochemical labeling of the SOD isoforms and nitro-tyrosine proteins. We found that aging is associated with increased levels of cellular superoxide and mitochondrial ROS concomitant with a reduction in Cu/Zn-SOD protein expression and total SOD enzymatic activity in MLV. This increase in oxidative stress and decrease in antioxidant activity was associated with evidence of increased lipid (as indicated by TBARS) and protein (as indicated by nitro-tyrosine labeling) oxidative damage.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>Thus for the first time, we demonstrate that aging-associated increases in oxidative stress and oxidative damage is indeed present in the walls of MLV and may contribute to the aging-associated lymphatic pump dysfunction we previously reported.</p>
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