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首页> 外文期刊>Journal of Cellular Physiology >Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes.
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Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes.

机译:酪氨酸激酶参与表达式诱导一氧化氮合酶在人类关节软骨细胞。

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摘要

The present study characterizes mechanisms involved with the induction of nitric oxide (NO) production, nitric oxide synthase (NOS) enzymatic activity and mRNA expression in human articular chondrocytes. Activation of chondrocytes with lipopolysaccharide (LPS) or IL-1 resulted in time- and dose-dependent increases in iNOS mRNA followed by increased NOS enzymatic activity and NO release. The protein tyrosine kinase (PTK) inhibitors herbimycin A or genistein reduced IL-1 or LPS-induced NO release and NOS enzymatic activity. This was associated with inhibition of iNOS mRNA expression as determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. In contrast, inhibitors of protein kinase C (PKC) or protein kinase A (PKA) did not affect these responses. These results were confirmed in experiments with second messenger agonists where neither activation of PKC, nor increases in cyclic adenosine monophosphate (cAMP) or increased intracellular calcium levels were associatedwith the induction of iNOS mRNA or NO release. These results suggest that PKC, PKA and calcium-dependent signals are not required or sufficient for the stimulation of NO production. However, NO production is dependent on tyrosine kinases due to their role in the expression of iNOS mRNA.
机译:本研究描述机制参与诱导一氧化氮(NO)生产、一氧化氮合酶(NOS)的酶在人类关节活动和mRNA的表达软骨细胞。脂多糖(LPS)和il - 1导致时间和剂量依赖性增加伊诺信使rna其次是增加NOS和酶的活动没有释放。抑制剂herbimycin或染料木黄酮降低il - 1或LPS-induced没有释放和NOS酶活动。伊诺mRNA表达由逆转聚合酶链反应(rt - pcr),和原位杂交。蛋白激酶C (PKC)或蛋白的抑制剂激酶(PKA)并不影响这些反应。这些结果在实验证实第二信使受体激动剂的地方激活PKC、增加循环腺苷酸(营)或增加与细胞内钙水平伊诺mRNA的感应或没有释放。结果表明,PKC, PKA和不需要或calcium-dependent信号没有足够的刺激生产。然而,没有生产依赖于酪氨酸激酶由于他们在表达中的作用

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