Differential activation of ERK 1/2 and JNK in normal human fibroblast-likecells in response to UVC radiation under different oxygen tensions

The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting bio logical functions are not well understood. We investigated whether the leve l of oxygen tension of culture was responsible for the differential activat ion of MAPK and different cellular outcomes in UVC-irradiated cells, The in tracellular oxidative level of normal human fibroblast-like cells in a norm al atmosphere (normoxic, 20% O-2) was increased within 30 min after UVC irr adiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N-acetyl-L-cysteine (NAC) or under physiologically hypoxi c (5% O-2) conditions, the elevation of the oxidative level by W-irradiatio n was significantly reduced. Among MAPK, extracellular-signal related kinas e (ERK) 1/2 was activated by UV regardless of the oxidative level, while c- Jun N-terminal kinase (JNK) activation was inhibited in NAG-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there w as less apoptosis and cell survival was enhanced. These results suggest tha t UV-induced oxidative stress was responsible for intracellular signaling t hrough the JNK pathway. Furthermore, the balance between ERK1/2 and JNK act ivities after UV irradiation under different oxygen tensions possibly modif ied cellular outcome in response to UV.