Effect of nitric oxide on mitogen-activated protein kinases in neonatal pulmonary vascular smooth muscle.
Effect of nitric oxide on mitogen-activated protein kinases in neonatal pulmonary vascular smooth muscle.
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一氧化氮对新生儿肺血管平滑肌丝裂原激活蛋白激酶的影响。
DOI：
10.1007/s00408-005-2545-4
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发表时间：
2005
期刊：
影响因子：
5
通讯作者：
Barman,ScottA
中科院分区：
文献类型：
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作者：
Barman,ScottA
丝裂原激活蛋白激酶 (MAPK) 属于丝氨酸/苏氨酸激酶，可响应生长因子刺激而快速激活。在成年哺乳动物细胞中，MAPK 家族包括细胞外信号调节激酶 1 和 2（ERK1 和 ERK2 或 p44mapk 和 p42mapk），它们易位到细胞核并整合来自第二信使的信号，导致细胞增殖或分化。然而，MAPKs在新生儿肺血管平滑肌中的具体作用尚不清楚。通过Western免疫印迹分析鉴定新生（1-2日龄）大鼠原代培养的肺血管平滑肌细胞p44mapk和p42mapkin的表达。用 10 nM 内皮素-1 (ET-1)（一种具有血管有丝分裂特性的强效血管收缩剂）治疗，可诱导 p44mapk 和 p42mapk 磷酸化，但用外源一氧化氮 (NO) 供体硝普钠治疗可抑制 ET-1 引起的 p44mapk 和 p42mapk 磷酸化。特异性 cGMP 依赖性蛋白激酶 (PKG) 抑制剂 KT5823、非特异性一氧化氮合酶 (NOS) 抑制剂 L-NAME 和特异性 NOS 1 阻断剂 NPLA 均显着增强 ET-1 引起的 p44mapk 和 p42mapk 磷酸化。总的来说，这些数据证明了大鼠新生肺血管平滑肌中特定 MAPK 的表达和磷酸化，并表明 NO 信号通路通过 ET-1 调节 MAPK 激活。
Mitogen-activated protein kinases (MAPKs) belong to the group of serine/threonine kinases that are rapidly activated in response to growth factor stimulation. In adult mammalian cells, the MAPK family includes extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2 or p44mapkand p42mapk), which translocate to the nucleus and integrate signals from second messengers leading to cellular proliferation or differentiation. However, the specific role of MAPKs in neonatal pulmonary vascular smooth muscle is not well understood. Expression of p44mapkand p42mapkin primary cultured pulmonary vascular smooth muscle cells from neonatal (1–2 day old) rats was identified by Western immunoblot analysis. Treatment with 10 nM endothelin-1 (ET-1), a potent vasoconstrictor with vascular mitogenic properties, induced phosphorylation of both p44mapkand p42mapk, but treatment with the exogenous nitric oxide (NO) donor sodium nitroprusside inhibited both p44mapkand p42mapkphosphorylation by ET-1. The specific cGMP-dependent protein kinase (PKG) inhibitor KT5823, the nonspecific nitric oxide synthase (NOS) inhibitorL-NAME, and the specific NOS 1 blocker NPLA all significantly enhanced both p44mapkand p42mapkphosphorylation by ET-1. Collectively, these data demonstrate the expression and phosphorylation of specific MAPKs in rat neonatal pulmonary vascular smooth muscle and suggests that the NO signaling pathway modulates MAPK activation by ET-1.