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Effects of chemopreventive selenium compounds on Jun N-kinase activities
V Adler1, M R Pincus, S Posner
1Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY 10595, USA.
Abstract:
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.
Insights
The organoselenium compound p-XSC modulates Jun-N-kinases (JNK) activation. Low doses potentiate UV-induced JNK activity, while higher doses inhibit it, suggesting a role in cellular stress response.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Jun-N-kinases (JNK) are crucial signaling molecules activated by various stressors like UV radiation.
- Organoselenium compounds are investigated for their chemopreventive properties.
Purpose of the Study:
- To investigate the effect of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on UV-mediated JNK activation in mouse fibroblasts.
- To elucidate the mechanism by which p-XSC modulates JNK signaling.
Main Methods:
- Utilized mouse fibroblasts as a model system.
- Administered varying concentrations of p-XSC before UV irradiation.
- Assessed JNK activity and its association with p21ras.
Main Results:
- Low concentrations (1-10 microM) of p-XSC potentiated UV-induced JNK activation.
- Higher doses of p-XSC showed a dose-dependent decrease in UV-mediated JNK activation.
- p-XSC also induced src-related tyrosine kinases and potentiated JNK-p21ras association.
Conclusions:
- p-XSC differentially modulates JNK activation in response to UV irradiation.
- The compound's ability to alter JNK activity and protein interactions suggests a role in cellular stress adaptation.