Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes
Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes
复制标题
DOI：
10.1111/1523-1747.ep12292595
复制
发表时间：
1997-06-01
影响因子：
6.5
通讯作者：
Agostinis, P
中科院分区：
文献类型：
--
作者：
Assefa, Z;Garmyn, M;Agostinis, P
哺乳动物细胞暴露于太阳紫外线（UV）辐射导致几种基因的表达，并且UV已被认为是皮肤癌的主要引发剂和促进剂。对人类皮肤恶性肿瘤贡献最大的太阳辐射成分是UVB（280-320 nm），其次是UVA（320-400 nm），而高能UVC（100-280 nm）被地球高层大气吸收。亚致死剂量的UVB在包括人原代角质形成细胞在内的几种细胞中产生c-jun和c-fos转录物的强烈诱导。本报告证实，这也是在HaCaT细胞系的情况下，并表明，类似的UVB剂量是有效的诱导剂的JNK/SAPK家族的促分裂原活化蛋白激酶，但只有弱激活剂的ERK。表皮生长因子（EGF）引起快速诱导JNK和ERK信号通路，EGF预处理下调EGF信号通路抑制UVB诱导的JNK 1活化。细胞的先前UVB照射通过随后的EGF处理降低了ERK 2活化的水平，但这使细胞敏化，并允许在用UVB或EGF再激发后JNK 1的超活化。抗氧化剂N-乙酰半胱氨酸损害UVB和EGF诱导的JNK 1活化。我们的数据表明，在UVB和EGF诱导的细胞反应途径中存在共享的信号成分，并暗示氧化应激在UVB和EGF激活JNK 1中起着重要作用。
Exposure of mammalian cells to solar ultraviolet (UV) radiation leads to the expression of several genes, and UV has been recognized as a major initiator and promoter of skin cancer. The component of the solar radiation that contributes most to human skin malignancy is UVB (280-320 nm) and, to a lesser extent, UVA (320-400 nm), whereas the high-energy UVC (100-280 nm) is absorbed by the earth's upper atmosphere. Sublethal doses of UVB produce strong induction of c-jun and c-fos transcripts in several cells including human primary keratinocytes. The present report confirms that this is also the case in the HaCaT cell line and shows that similar UVB doses are potent inducers of the JNK/SAPK family of mitogen-activated protein kinases but only weak activators of ERKs. Epidermal growth factor (EGF) caused rapid induction of both JNK- and ERK-signaling pathways, and the downmodulation of the EGF-signaling pathway by EGF pre-treatment inhibited the UVB-induced JNK1 activation. Prior UVB irradiation of the cells decreased the level of the ERK2 activation by a subsequent EGF treatment, but this sensitized the cells and allowed for the super-activation of JNK1 after a rechallenge with either UVB or EGF. The antioxidant N-acetylcysteine impaired the UVB- and EGF-induced activation of JNK1. Our data suggest the presence of shared signaling component(s) in the UVB- and EGF-induced cellular response pathways and imply that oxidative stress plays a significant role in the activation of JNK1 by UVB and EGF.