Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells
Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells
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DOI：
10.1291/hypres.24.251
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Tamaki, T
中科院分区：
文献类型：
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作者：
Kyaw, M;Yoshizumi, M;Tamaki, T
血管紧张素II （angii）诱导血管平滑肌细胞（VSMC）肥大，导致多种心血管疾病。Ang ii诱导的细胞事件部分是由活性氧（ROS）介导的，活性氧也涉及有丝分裂原活化蛋白（MAP）激酶的激活。尽管已经提出抗氧化剂的治疗性管理对血管疾病有用，但调节ROS敏感信号事件的确切机制尚未得到很好的表征。因此，我们假设抗氧化剂可能影响Ang II诱导的ros介导的MAP激酶激活。目前的研究结果表明，Ang II刺激培养的大鼠主动脉平滑肌细胞（RASMC）中ERK 1/2、JNK和p38 MAPK的快速和显著激活，Ang II诱导的ERK 1/2激活不受所有抗氧化剂的影响，而JNK对所有抗氧化剂都敏感。相反，DPI和抗坏血酸对p38 MAPK的激活具有浓度依赖性，而NAC仅在高浓度时对p38 MAPK的激活具有抑制作用。DETC和Trolox C对Ang II激活p38 MAPK没有影响。我们进一步研究了抗氧化剂对Ang ii诱导的氧消耗增加的影响，作为RASMC中ROS生成的指标。DPI强烈抑制Ang ii诱导的耗氧量增加。DETC也抑制了Ang ii诱导的氧消耗，而抗坏血酸则显著增强了它。这些发现表明，抗氧化剂对VSMC中MAP激酶活化的抑制作用部分可归因于其对VSMC中Ang II生成ROS的调节作用，因此，抗氧化剂对MAP激酶的抑制可能暗示其对心血管疾病的缓解作用。
Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in several cardiovascular diseases. Ang Ii-induced cellular events have been mediated, in part, by reactive oxygen species (ROS) which also involve activation of mitogen-activated protein (MAP) kinases, Although it has been proposed that the therapeutic administration of antioxidants is useful for vascular diseases, the precise mechanisms which regulate ROS-sensitive signaling events have not been well characterized. Thus, we hypothesized that antioxidants may affect ROS-mediated MAP kinases activation induced by Ang II, The present findings showed that Ang II stimulated rapid and significant activation of ERK 1/2, JNK and p38 MAPK in cultured rat aortic smooth muscle cells (RASMC), Ang Ii-induced ERK 1/2 activation was not affected by all antioxidants examined, whereas JNK was sensitive to all antioxidants. In contrast, p38 MAPK activation was inhibited by DPI and ascorbic acid concentration-dependently, but by NAC only at high concentration. DETC and Trolox C had no effects on p38 MAPK activation by Ang II. We further examined the effects of antioxidants on Ang Ii-induced increases in oxygen consumption as an index of ROS generation in RASMC. DPI strongly inhibited Ang Ii-induced increases in oxygen consumption. DETC also inhibited Ang II-induced oxygen consumption, whereas ascorbic acid markedly augmented it. These findings suggest that the inhibitory effects of antioxidants on MAP kinases activation in VSMC are attributable, in part, to their modulating effects on ROS generation by Ang II in VSMC, Thus, inhibition of MAP kinases by antioxidants may imply their usefulness for relief of cardiovascular diseases.