Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2
Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2
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DOI：
10.1152/ajplung.1997.273.5.l1029
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发表时间：
1997-11-01
影响因子：
4.9
通讯作者：
Mossman, BT
中科院分区：
文献类型：
--
作者：
Jimenez, LA;Zanella, C;Mossman, BT
氧化剂对细胞信号转导通路的刺激可能在肺和胸膜疾病的发病机制中起重要作用。在这里，我们证明了在大鼠胸膜间皮细胞中，凋亡浓度的青石棉和过氧化氢诱导细胞外信号调节蛋白激酶(ERK)的磷酸化和激活。H_2O_2还激活了c-Jun-NH_2末端蛋白激酶(JNK)/应激激活的蛋白激酶。相反，石棉引起更长时间的ERK激活，而不是JNK激活。过氧化氢酶可消除过氧化氢和石棉对ERK的激活作用。此外，青石棉纤维表面铁的螯合或N-乙酰-L半胱氨酸的加入可阻止青石棉激活ERK和诱导细胞凋亡，这可能是细胞信号转导的氧化机制。蛋白酪氨酸激酶1抑制剂PD-98059阻断了石棉诱导的细胞凋亡，证实了ERK激活与细胞凋亡之间的因果关系。这些结果表明，在氧化应激引起的表型反应中，不同的细胞信号级联可能是重要的。
Stimulation of cell signaling cascades by oxidants may be important in the pathogenesis of pulmonary and pleural diseases. Here, we demonstrate in rat pleural mesothelial cells that apoptotic concentrations of crocidolite asbestos and H2O2 induce phosphorylation and activation of extracellular signal-regulated protein kinases (ERK). Activation of c-jun-NH2-terminal protein kinases (JNK)/stress-activated protein kinases was also observed in response to H2O2. In contrast, asbestos caused more protracted activation of ERK without JNK activation. Both H2O2- and asbestos-induced activation of ERK was abolished by catalase. Moreover, chelation of surface iron from crocidolite fibers or addition of N-acetyl-L-cysteine prevented ERK activation and apoptosis by crocidolite, indicating an oxidative mechanism of cell signaling. The MEK1 inhibitor PD-98059 abrogated asbestos-induced apoptosis, confirming a causal relationship between ERK activation and apoptosis. These results suggest that distinct cell-signaling cascades may be important in phenotypic responses elicited by oxidant stresses.