T0901317, an LXR agonist, augments PKA-induced vascular cell calcification.
T0901317, an LXR agonist, augments PKA-induced vascular cell calcification.
复制标题
DOI：
10.1016/j.febslet.2009.03.039
复制
发表时间：
2009-04-17
期刊：
影响因子：
3.5
通讯作者：
Tintut, Yin
中科院分区：
文献类型：
--
作者：
Hsu, Jeffrey J.;Lu, Jinxiu;Huang, Michael S.;Geng, Yifan;Sage, Andrew P.;Bradley, Michelle N.;Tontonoz, Peter;Demer, Linda L.;Tintut, Yin
我们研究了LXR激动剂对动脉粥样硬化病变中常见的血管钙化的影响。T0901317（一种LXR激动剂）增强了从野生型小鼠分离的主动脉平滑肌细胞中蛋白激酶A（PKA）诱导的矿化和碱性磷酸酶（ALP）活性，但不增强Lxrβ-/-小鼠的活性。6小时的T0901317处理增强了PKA诱导的磷酸盐转运蛋白Pit-1的表达，Pit-1是矿化的正调节因子，表明了直接作用。10天T0901317处理减弱了PKA诱导的矿化抑制剂、骨桥蛋白和外核苷酸焦磷酸酶/磷酸二酯酶-1的表达，表明了间接作用。T0901317的作用通过抑制ALP、Pit-1和Rho相关激酶而减弱，但不通过抑制PKA而减弱。这些结果表明，T0901317增强的矿化发生在PKA下游，涉及直接和间接LXR介导的途径。
We examined the effect of LXR agonists on vascular calcification, prevalent in atherosclerotic lesions. T0901317, an LXR agonist, augmented protein kinase A (PKA)-induced mineralization and alkaline phosphatase (ALP) activity in aortic smooth muscle cells isolated from wild-type, but not from Lxrβ-/- mice. A six-hour T0901317 treatment augmented the PKA-induced expression of the phosphate transporter Pit-1, a positive regulator of mineralization, suggesting a direct role. A ten-day T0901317 treatment attenuated PKA-induced expression of mineralization inhibitors, osteopontin and ectonucleotide pyrophosphatase/phosphodiesterase-1, suggesting an indirect role. The effects of T0901317 were attenuated by inhibition of ALP, Pit-1 and Rho-associated kinase, but not by inhibition of PKA. These results suggest that T0901317-augmented mineralization occurs downstream of PKA, involving both direct and indirect LXR-mediated pathways.
登录
查看更多内容
影响因子：
20.1
作者：
Li, XW;Yang, HY;Giachelli, CM
通讯作者：
Giachelli, CM
影响因子：
6.2
作者：
Johnson, K;Goding, J;Terkeltaub, R
通讯作者：
Terkeltaub, R
影响因子：
13.2
作者：
Giachelli, CM;Jono, S;Morii, H
通讯作者：
Morii, H
DOI：
10.1161/atvbaha.107.153668
发表时间：
2007-12-01
影响因子：
8.7
作者：
Al-Aly, Ziyad;Shao, Jian-Su;Towler, Dwight A.
通讯作者：
Towler, Dwight A.
影响因子：
3.5
作者：
Terasaka, N;Hiroshima, A;Inaba, T
通讯作者：
Inaba, T