The redox active components H2O2 and N-acetyl-L-cysteine regulate expression of c-jun and c-fos in lens systems.
The redox active components H2O2 and N-acetyl-L-cysteine regulate expression of c-jun and c-fos in lens systems.
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DOI：
10.1006/exer.1994.1096
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发表时间：
1994-08
影响因子：
3.4
通讯作者：
Wan-cheng Li;Guo-ming Wang;Ren-Rong Wang;A. Spector
中科院分区：
文献类型：
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作者：
Wan-cheng Li;Guo-ming Wang;Ren-Rong Wang;A. Spector
过氧化氢（H2 O2）与人类白内障的发展有关。在分子水平上，已经观察到H2 O2对DNA、蛋白质和脂质造成损伤。现在首次证明，在透镜系统中，白内障患者中发现的浓度的H2 O2诱导c-jun和c-fos的表达。在最佳浓度的H2 O2，mRNA积累的c-jun和c-fos在大鼠晶状体中的诱导20倍和18倍以上的正常水平分别，但具有不同的动力学。这种诱导发生在转录水平。H2 O2还通过激活兔透镜上皮细胞中的激活蛋白-1（AP-1）诱导反式激活。抗氧化剂N-乙酰半胱氨酸（NAC）对c-jun和c-fos的诱导具有双重作用。用5 mM NAC预孵育大鼠晶状体抑制H2 O2诱导，而30 mM和50 mM NAC诱导这些基因的表达并掩盖H2 O2效应。H7（50 μ M）、染料木黄酮（2 μ M）和冈田酸（20 nM）均阻断H2 O2处理的大鼠晶状体中c-jun和c-fos mRNA积累的诱导。这些结果表明，H_2O_2激活蛋白激酶和磷酸酶依赖的信号转导通路，诱导c-jun和c-fos的表达，从而可能调控透镜晶体蛋白基因和其他含有AP-1结合位点的基因。
Hydrogen peroxide (H2O2) is implicated in human cataract development. At the molecular level H2O2 has been observed to cause damage to DNA, protein and lipid. It is now demonstrated, for the first time in a lens system, that H2O2 at concentrations found in cataract patients induces expression of both c-jun and c-fos. At optimal concentrations of H2O2, mRNA accumulation of c-jun and c-fos in the rat lenses is induced 20- and 18-fold above normal levels respectively, but with distinct kinetics. This induction occurs at the transcriptional level. H2O2 also induces transactivation by activating protein-1 (AP-1) in rabbit lens epithelial cells. The antioxidant N-acetyl-cysteine (NAC) has a dual effect on the induction of c-jun and c-fos. Preincubation of rat lenses with 5 mM NAC inhibits the induction by H2O2, while 30 mM and 50 mM NAC induce expression of these genes and mask the H2O2 effect. H7 (50 microM), genistein (2 microM) and okadaic acid (20 nM), all block the induction of c-jun and c-fos mRNA accumulation in the H2O2-treated rat lenses. These results suggest that H2O2 activates protein kinase and phosphatase dependent signal transduction pathways to induce c-jun and c-fos expression which may regulate lens crystallin genes and other genes containing AP-1 binding sites.