Hyper‐reactivity of diacylglycerol kinase is involved in the dysfunction of aortic smooth muscle contractility in streptozotocin‐induced diabetic rats
Hyper‐reactivity of diacylglycerol kinase is involved in the dysfunction of aortic smooth muscle contractility in streptozotocin‐induced diabetic rats
复制标题
二酰甘油激酶的高反应性与链脲佐菌素诱导的糖尿病大鼠主动脉平滑肌收缩功能障碍有关
DOI：
--
复制
发表时间：
2002
影响因子：
7.3
通讯作者：
K. Momose
中科院分区：
文献类型：
--
作者：
K. Nobe;Y. Sakai;Yoshiaki Maruyama;K. Momose
糖尿病患者血管收缩功能障碍已有报道，但其机制尚不清楚。在本研究中，在链脲佐菌素诱导的糖尿病大鼠主动脉中检测到钙增敏作用，包括收缩增加。我们假设细胞内信号系统的改变在糖尿病血管收缩功能障碍中起作用。因此，对作为磷脂酰肌醇(PI)代谢关键酶的双甘油(DG)激酶进行了研究。去甲肾上腺素(NE)可引起对照组大鼠DG激酶的时间和剂量依赖性激活。这种激活需要同时增加细胞内钙离子浓度([Ca2+]i)和蛋白激酶C(PKC)的激活。在糖尿病大鼠，观察到DG激酶的高反应性，包括静息状态下的失活和NE刺激时的过度激活。在高反应过程中，DG激酶对[Ca~(2+)]i的依赖性增强。用50 mM KCl处理后，PKC的活性显著升高；此外，只有糖尿病患者才能检测到PKC的基础激活。这些结果表明，PKC在静息状态下已被激活。相反，由于没有[Ca~(2+)]i升高，这些条件不足以激活DG激酶。在NE刺激过程中，PKC活性维持不变，[Ca~(2+)]i升高。因此，DG激酶被激活，钙依赖的增加加强了这种激活。本研究提示，糖尿病患者的DG激酶高反应性与细胞内[Ca~(2+)]i升高和PKC基础激活有关。这种现象可能与糖尿病患者血管收缩增加有关，这种收缩是由PI-周转加速引起的。
Dysfunction of vascular contraction in diabetes has been reported; however, the mechanisms are poorly understood. In this study, calcium sensitization involving increases in contraction in streptozotocin‐induced diabetic rat aorta was detected. We hypothesize that an alteration in the intracellular signalling system plays a role in the dysfunction of vascular contractility in diabetes. Therefore, diacylglycerol (DG) kinase as a key enzyme of phosphatidylinositol (PI) turnover was investigated. Treatment with norepinephrine (NE) caused time‐ and dose‐dependent activation of DG kinase in control rats. This activation required simultaneous increases in intracellular calcium concentration ([Ca2+]i) and protein kinase C (PKC) activation. In diabetic rats, hyper‐reactivity of DG kinase involving inactivation in the resting state and over‐activation in NE stimulation was observed. During hyper‐reactivity, [Ca2+]i dependency of DG kinase was enhanced. Treatment with 50 mM KCl induced significant escalation in activity; moreover, basal activation of PKC was detected only in diabetes. These results suggested that PKC had been activated in the resting state. In contrast, these conditions were insufficient for DG kinase activation due to the absence of [Ca2+]i elevation. During NE‐stimulation, PKC activation was maintained and [Ca2+]i increased. Therefore, DG kinase was activated and an elevation in calcium dependency enhanced this activation. The present study suggested that DG kinase hyper‐reactivity in diabetes involved both an increase in [Ca2+]i and basal activation of PKC. This phenomenon may be associated with increased vascular contraction in diabetes mediated by acceleration of PI‐turnover.
新霉素抑制子宫肌组织中激素刺激的平滑肌收缩。
影响因子：
3.1
作者：
Phillippe,M
通讯作者：
Phillippe,M