Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins
Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins
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DOI：
10.1152/ajpregu.2000.279.2.r492
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发表时间：
2000-08-01
影响因子：
2.8
通讯作者：
Brophy, C
中科院分区：
文献类型：
--
作者：
Fuchs, LC;Giulumian, AD;Brophy, C
环核苷酸依赖的血管松弛与小分子热休克蛋白(HSP)HSP20的磷酸化增加有关。另一种小分子热休克蛋白HSP27的磷酸化增加与环核苷酸依赖性血管松弛受损有关。在体外，热休克蛋白的表达可以通过暴露于几种类型的细胞应激而改变。为了确定体内行为应激是否改变了小HSPs的血管表达和磷酸化以及环核苷酸依赖的血管松弛，对临界高血压大鼠进行了束缚应激并暴露于空气喷射应激2 h/d，连续10天或将其留在家中。应激损伤主动脉对Forsklin和硝普钠的松弛，Forsklin和硝普钠分别激活腺酰环化酶和鸟苷酸环化酶。这与主动脉HSP27的表达和磷酸化增加有关，HSP27定位于血管平滑肌，但磷酸化(P)-HSP20的数量减少。为了确定P-HSP27是否抑制HSP20的磷酸化，将P-HSP27加入含有重组HSP20和cAMP依赖的蛋白激酶催化亚单位的反应混合物中。P-HSP27以浓度依赖的方式抑制HSP20的磷酸化。这些数据表明，P-HSP27可以抑制HSP20的磷酸化。P-HSP27的增加和P-HSP20的减少与在体行为应激反应中环核苷酸依赖的血管平滑肌松弛减少有关，这一效应与之前在体外观察到的细胞应激反应相似。
Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.