TY - JOUR
T1 - Dose rate and mode of exposure are key factors in JNK activation by UV irradiation
AU - Adler, Victor
AU - Polotskaya, Alla
AU - Kim, Jeannette
AU - Dolan, Lisa
AU - Davis, Roger
AU - Pincus, Matthew
AU - Ronai, Ze'ev
N1 - Funding Information:
We thank J.Pelling and D.Birt for providing us with the UVB filter and C.Basilico for NIH 3T3-4A cells. Use Hoffmann for editorial assistance and Roz Alexander for typing this manuscript. Support from NCI grants CA 51995 and CA 59908 is gratefully acknowledged
PY - 1996/9
Y1 - 1996/9
N2 - Single exposure of cells to UVC (254 nm for 30 s) or to UVB (300 nm for 10 min) was shown to activate jun-NH2 kinases which, in turn, phosphorylate their substrates ELK-1, c-jun and ATF-2. While UVC (40-80 J/m2) activates JNK up to 4 h, with maximal induction after 30 min, UVB (150-300 J/m2) activates JNK over a prolonged period, up to 24 h, with maximal induction after 6 h. UV-mediated activation of src-related tyrosine kinases and MAPK revealed different kinetics, with maximal induction after 24 h. As recent studies had indicated a role of a WC component in mediating the ability of UVB to activate JNK, we have examined the effect of dose rate as well as of multiplicity of exposures on the activation of these kinases. The UVC portion found in 300 J/m2 UVB (5%, corresponding to 15 J/m2, administered within 10 s) did not activate JNK. However, when the same dose was administered at a lower rate (i.e. over 10 min, as needed for UVB irradiation) it was found capable of activating JNK, MAPK and src kinases, but to a lower degree and with different kinetics than found for UVB. Such differences point to cellular changes which are elicited by UVB, but not UVC. Although a single UVB exposure using a filter that blocks wavelengths below 300 nm prevented activation of JNK, multiple exposures of filtered UVB wavelengths (mimicking chronic exposure) were able to activate JNK. We conclude that the mode of UVB exposure (dose rate and multiplicity) is a crucial determinant for physiologically relevant activation of JNK.
AB - Single exposure of cells to UVC (254 nm for 30 s) or to UVB (300 nm for 10 min) was shown to activate jun-NH2 kinases which, in turn, phosphorylate their substrates ELK-1, c-jun and ATF-2. While UVC (40-80 J/m2) activates JNK up to 4 h, with maximal induction after 30 min, UVB (150-300 J/m2) activates JNK over a prolonged period, up to 24 h, with maximal induction after 6 h. UV-mediated activation of src-related tyrosine kinases and MAPK revealed different kinetics, with maximal induction after 24 h. As recent studies had indicated a role of a WC component in mediating the ability of UVB to activate JNK, we have examined the effect of dose rate as well as of multiplicity of exposures on the activation of these kinases. The UVC portion found in 300 J/m2 UVB (5%, corresponding to 15 J/m2, administered within 10 s) did not activate JNK. However, when the same dose was administered at a lower rate (i.e. over 10 min, as needed for UVB irradiation) it was found capable of activating JNK, MAPK and src kinases, but to a lower degree and with different kinetics than found for UVB. Such differences point to cellular changes which are elicited by UVB, but not UVC. Although a single UVB exposure using a filter that blocks wavelengths below 300 nm prevented activation of JNK, multiple exposures of filtered UVB wavelengths (mimicking chronic exposure) were able to activate JNK. We conclude that the mode of UVB exposure (dose rate and multiplicity) is a crucial determinant for physiologically relevant activation of JNK.
UR - http://www.scopus.com/inward/record.url?scp=0029814281&partnerID=8YFLogxK
U2 - 10.1093/carcin/17.9.2073
DO - 10.1093/carcin/17.9.2073
M3 - Article
C2 - 8824537
AN - SCOPUS:0029814281
SN - 0143-3334
VL - 17
SP - 2073
EP - 2076
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -