Li Qiurong, Zhang Qiang, Wang Meng, Liu Fuzhong, Zhao Sumin, Ma Jian, Luo Nan, Li Ning, Li Yousheng, Xu Guowang, Li Jieshou
Institute of General Surgery, Jinling Hospital, Nanjing, China.
Arch Biochem Biophys. 2007 Oct 15;466(2):250-9. doi: 10.1016/j.abb.2007.06.023. Epub 2007 Jun 29.
n-3 Polyunsaturated fatty acids are assumed to play an important role in the prevention and treatment of atherosclerosis. Endothelial nitric-oxide synthase (eNOS) is responsible for cardiovascular homeostasis involving in regulation of vascular function, and the subcellular localization is critical for its activation. Here we determined the effect of docosahexaenoic acid (DHA, 22:6 n-3) on distribution of eNOS and its activity. DHA treatment markedly altered lipid environment of caveolae microdomains, which was coincided with selective displacement of caveolin-1 and eNOS from caveolae. Akt was not detected in caveolae fractions and CaM was distributed in both of caveolin-1-enriched membranes and non-caveolar fractions, whose distribution was unaffected by DHA. These data demonstrated for the first time that DHA altered caveolae microenvironment not only by modifying membrane lipid composition, but also by changing distribution of major structural proteins. DHA-induced alterations in caveolae lipid/protein environment may be an important mechanism in the development of pathogenesis of atherosclerosis.
n-3多不饱和脂肪酸被认为在动脉粥样硬化的预防和治疗中发挥重要作用。内皮型一氧化氮合酶（eNOS）负责心血管稳态，参与血管功能调节，其亚细胞定位对其激活至关重要。在此，我们确定了二十二碳六烯酸（DHA，22:6 n-3）对eNOS分布及其活性的影响。DHA处理显著改变了小窝微区的脂质环境，这与小窝蛋白-1和eNOS从小窝中选择性移位相吻合。在小窝组分中未检测到Akt，钙调蛋白分布于富含小窝蛋白-1的膜和非小窝组分中，其分布不受DHA影响。这些数据首次证明，DHA不仅通过改变膜脂质组成，还通过改变主要结构蛋白的分布来改变小窝微环境。DHA诱导的小窝脂质/蛋白质环境改变可能是动脉粥样硬化发病机制发展中的一个重要机制。
