The antiapoptotic effect of low-dose UVB irradiation in NIH3T3 cells involves caspase inhibitions.
UVB irradiation is a well-known apoptosis induction factor. However, we have previously found that low doses of UVB irradiation inhibited apoptosis induced by both serum starvation and lack of extracellular matrix, involving a significant inhibition of caspase-3/7 activation. In this study, we report on the relationship between the UVB-induced anti-apoptotic effect and caspase-3/7 inhibition by reactive oxygen species (ROS). The UVB-induced antiapoptotic effect was partially prevented by an antioxidant agent, N-acetylcysteine. A ROS-generating agent, menadione and a pro-oxidant agent, H2O2 also showed an effect that was similar to the UVB-induced antiapoptotic effect, indicating that ROS contributed to the antiapoptotic effect. UVB irradiation significantly suppressed caspase-3/7 activation, which was caused by the inhibition of proteolysis and not by the inhibition of enzymatic activity itself. The prevention of proteolysis was also confirmed by both the following results: one is the inhibition of in vitro caspase-3/7 and -9 activation in cell lysates exposed to UVB in the presence of cytochrome c and dATP, which was caused by the production of ROS, and the other is the inhibition of in vitro caspase-3/7 activation in the presence of active caspase-9. These results showed that the inhibition of the caspase cascade downstream mitochondria by ROS production, leading to a significant inhibition of caspase-3/7 activation, was one of the causes of the antiapoptotic effect by small doses of UVB irradiation.
Ibuki
Yuko
Y
Laboratory of Radiation Biology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada, Shizuoka-shi, Japan. ibuki@sea.u-shizuoka-ken.ac.jp
Goto
Rensuke
R
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D051379:Mice; D018462:Photobiology; D017382:Reactive Oxygen Species / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; D020169:Caspases