Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease.
Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease.
复制标题
DOI：
10.1016/j.freeradbiomed.2009.11.014
复制
发表时间：
2010-02-15
影响因子：
7.4
通讯作者：
Lundberg, Jon O.
中科院分区：
文献类型：
--
作者：
Borniquel, Sara;Jansson, Emmelie A.;Cole, Marsha P.;Freeman, Bruce A.;Lundberg, Jon O.
一氧化氮及其代谢产物在氧化性炎症条件下与不饱和脂肪酸发生硝化反应，形成亲电硝基脂肪酸衍生物。这些内源性亲电介质激活抗炎信号传递反应，作为过氧化物酶体增殖物激活受体γ(PPARγ)的高亲和力配体。在这里，我们研究了9-或10-硝基十八碳烯酸油酸(OA-NO2)和天然油酸(OA)在小鼠结肠炎模型中的治疗效果。OA-NO2降低疾病活动性指数，完全阻止葡聚糖硫酸钠诱导的结肠缩短和结肠p65表达增加。在给予OA-NO2后，可以观察到PPARγ在结肠样本和细胞中的表达增加，而OA对此没有影响。这种对PPARγ表达的诱导被PPARγ拮抗剂GW9662完全阻断。5-氨基水杨酸，一种常规用于炎症性肠病治疗的抗炎药物，也增加了PPARγ的表达，但幅度较小。总之，这些发现表明，在实验性炎症性肠病中，给予OA-NO2可以减轻结肠炎并改善临床症状。这种保护包括激活结肠PPARγ。
Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor γ (PPARγ). Here we examined the therapeutic effects of 9- or 10-nitro-octadecenoic oleic acid (OA-NO2) and native oleic acid (OA) in a mouse model of colitis. OA-NO2 reduced the disease activity index and completely prevented dextran sulfate sodium-induced colon shortening and the increase in colonic p65 expression. Increased PPARγ expression was observed in colon samples as well as in cells after OA-NO2 administration, whereas no effect was seen with OA. This induction of PPARγ expression was completely abolished by the PPARγ antagonist GW9662. 5-Aminosalicylic acid, an anti-inflammatory drug routinely used in the management of inflammatory bowel disease, also increased PPARγ expression but to a lesser extent. Altogether, these findings demonstrate that administration of OA-NO2 attenuates colonic inflammation and improves clinical symptoms in experimental inflammatory bowel disease. This protection involves activation of colonic PPARγ.
登录
查看更多内容
影响因子：
4.9
作者：
Saubermann, LJ;Nakajima, A;Blumberg, RS
通讯作者：
Blumberg, RS
DOI：
10.1073/pnas.0402587101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Baker, PRS;Schopfer, FJ;Freeman, BA
通讯作者：
Freeman, BA
影响因子：
4.8
作者：
Baker, Laura M. S.;Baker, Paul R. S.;Freeman, Bruce A.
通讯作者：
Freeman, Bruce A.
影响因子：
7.4
作者：
Schopfer, F. J.;Batthyany, C.;Freeman, B. A.
通讯作者：
Freeman, B. A.
影响因子：
4.8
作者：
Baker, PRS;Lin, YM;Freeman, BA
通讯作者：
Freeman, BA