Involvement of Lipid Peroxidation-Derived Aldehyde-protein Adducts in Autoimmunity Mediated by Trichloroethene. Export

@article{citeulike:3346874, abstract = {Lipid peroxidation, a major contributor to cellular damage, is also implicated in the pathogenesis of autoimmune diseases (AD). The focus of this study was to elucidate the role of lipid peroxidation-derived aldehydes in autoimmunity induced and/or exacerbated by chemical exposure. Previous studies showed that trichloroethene (TCE) is capable of inducing/accelerating autoimmunity. To test whether TCE-induced lipid peroxidation might be involved in the induction/exacerbation of autoimmune responses, groups of autoimmune-prone female MRL +/+ mice were treated with TCE (10 mmol/kg, i.p., every 4th day) for 6 or 12 wk. Significant increases of the formation of malondialdehyde (MDA)- and 4-hydroxynonenal (HNE)-protein adducts were found in the livers of TCE-treated mice at both 6 and 12 wk, but the response was greater at 12 wk. Further characterization of these adducts in liver microsomes showed increased formation of MDA-protein adducts with molecular masses of 86, 65, 56, 44, and 32 kD, and of HNE-protein adducts with molecular masses of 87, 79, 46, and 17 kD in TCE-treated mice. In addition, significant induction of anti-MDA- and anti-HNE-protein adduct-specific antibodies was observed in the sera of TCE-treated mice, and showed a pattern similar to MDA- or HNE-protein adducts. The increases in anti-MDA- and anti-HNE-protein adduct antibodies were associated with significant elevation in serum anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies at 6 wk and, to a greater extent, at 12 wk. These studies suggest that TCE-induced lipid peroxidation is associated with induction/exacerbation of autoimmune response in MRL+/+ mice, and thus may play an important role in disease pathogenesis. Further interventional studies are needed to establish a causal relationship between lipid peroxidation and TCE-induced autoimmune response.}, author = {Wang, Gangduo and Ansari, G. A. S. and Khan, Firoze M.}, citeulike-article-id = {3346874}, citeulike-linkout-0 = {http://lib.bioinfo.pl/pmid:17966069}, journal = {J Toxicol Environ Health}, keywords = {adducts, aldehydes, autoimmunity, lipid\_peroxidation, trichloroethene}, number = {23}, pages = {1977--1985}, posted-at = {2008-09-28 13:38:54}, priority = {3}, title = {Involvement of Lipid Peroxidation-Derived Aldehyde-protein Adducts in Autoimmunity Mediated by Trichloroethene.}, url = {http://lib.bioinfo.pl/pmid:17966069}, volume = {70}, year = {2007} }

TY - JOUR ID - citeulike:3346874 L3 - citeulike-article-id:3346874 N2 - Lipid peroxidation, a major contributor to cellular damage, is also implicated in the pathogenesis of autoimmune diseases (AD). The focus of this study was to elucidate the role of lipid peroxidation-derived aldehydes in autoimmunity induced and/or exacerbated by chemical exposure. Previous studies showed that trichloroethene (TCE) is capable of inducing/accelerating autoimmunity. To test whether TCE-induced lipid peroxidation might be involved in the induction/exacerbation of autoimmune responses, groups of autoimmune-prone female MRL +/+ mice were treated with TCE (10 mmol/kg, i.p., every 4th day) for 6 or 12 wk. Significant increases of the formation of malondialdehyde (MDA)- and 4-hydroxynonenal (HNE)-protein adducts were found in the livers of TCE-treated mice at both 6 and 12 wk, but the response was greater at 12 wk. Further characterization of these adducts in liver microsomes showed increased formation of MDA-protein adducts with molecular masses of 86, 65, 56, 44, and 32 kD, and of HNE-protein adducts with molecular masses of 87, 79, 46, and 17 kD in TCE-treated mice. In addition, significant induction of anti-MDA- and anti-HNE-protein adduct-specific antibodies was observed in the sera of TCE-treated mice, and showed a pattern similar to MDA- or HNE-protein adducts. The increases in anti-MDA- and anti-HNE-protein adduct antibodies were associated with significant elevation in serum anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies at 6 wk and, to a greater extent, at 12 wk. These studies suggest that TCE-induced lipid peroxidation is associated with induction/exacerbation of autoimmune response in MRL+/+ mice, and thus may play an important role in disease pathogenesis. Further interventional studies are needed to establish a causal relationship between lipid peroxidation and TCE-induced autoimmune response. IS - 23 JF - J Toxicol Environ Health EP - 1985 TI - Involvement of Lipid Peroxidation-Derived Aldehyde-protein Adducts in Autoimmunity Mediated by Trichloroethene. VL - 70 SP - 1977 KW - adducts KW - aldehydes KW - autoimmunity KW - lipid_peroxidation KW - trichloroethene AU - Wang, Gangduo AU - Ansari, GAS AU - Khan, Firoze PY - 2007/// UR - http://lib.bioinfo.pl/pmid:17966069 ER -