Effects of chemopreventive selenium compounds on Jun N-kinase activities.
Activation of Jun-N-kinases (JNK) is stimulated by diverse agents including UV-irradiation, heat shock, tumor necrosis factor and osmotic shock. In the present study we have elucidated the effect of the organoselenium chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC, on UV-mediated JNK activation. Using mouse fibroblasts as a model cell system we found that low concentrations (1-10 microM range) of p-XSC did not affect JNK activity, yet were capable of potentiating JNK activity when administered prior to UV-irradiation. While higher doses of p-XSC have minimal effect on JNK activation, when combined with UV, there is a dose-dependent decrease in JNK activation. Similar to its effects on JNK, p-XSC is a potent inducer of src-related tyrosine kinases. p-XSC mediated changes in JNK activation correlate with its ability to potentiate the association of JNK with p21ras, in a manner similar to that we have previously observed with GTP or sodium vanadate. That p-XSC can modulate JNK activities points to a possible mechanism by which it contributes to the cell's ability to cope with stress.
Adler
V
V
Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY 10595, USA.
Pincus
M R
MR
Posner
S
S
Upadhyaya
P
P
El-Bayoumy
K
K
Ronai
Z
Z
D016475:3T3 Cells; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006358:Hot Temperature; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D016566:Organoselenium Compounds / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays; D019061:src-Family Kinases / Q000378:metabolism
D016588:Anticarcinogenic Agents; D016566:Organoselenium Compounds; C074153:1,4-phenylenebis(methylene)selenocyanate; D019061:src-Family Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)