Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.
Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice sugges...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4043737?pdf=render |
| _version_ | 1818286856634105856 |
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| author | Gangduo Wang Jianling Wang Xuemei Luo G A Shakeel Ansari M Firoze Khan |
| author_facet | Gangduo Wang Jianling Wang Xuemei Luo G A Shakeel Ansari M Firoze Khan |
| author_sort | Gangduo Wang |
| collection | DOAJ |
| description | Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water). TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies. |
| first_indexed | 2024-12-13T01:31:15Z |
| format | Article |
| id | doaj.art-04f37f6910eb41b6bcb755b4646ba95d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T01:31:15Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-04f37f6910eb41b6bcb755b4646ba95d2022-12-22T00:03:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9866010.1371/journal.pone.0098660Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.Gangduo WangJianling WangXuemei LuoG A Shakeel AnsariM Firoze KhanExposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water). TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.http://europepmc.org/articles/PMC4043737?pdf=render |
| spellingShingle | Gangduo Wang Jianling Wang Xuemei Luo G A Shakeel Ansari M Firoze Khan Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. PLoS ONE |
| title | Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. |
| title_full | Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. |
| title_fullStr | Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. |
| title_full_unstemmed | Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. |
| title_short | Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. |
| title_sort | nitrosative stress and nitrated proteins in trichloroethene mediated autoimmunity |
| url | http://europepmc.org/articles/PMC4043737?pdf=render |
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