Dietary energy restriction inhibits ERK but not JNK or p38 activity in theepidermis of SENCAR mice

Ongoing studies in our laboratory have demonstrated that dietary energy res triction (DER) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 transcription factor binding to DNA in the epidermis of SENCAR mice. To dissect the specific signal transduction pathways through which DER inhi bits the AP-1:DNA binding, we analyzed the activities of three major MAP ki nases that lead to the induction of AP-1, The changes in ERK1 and ERK2 prot ein expression and phosphorylation were further characterized by western bl ot analysis. Female SENCAR mice were pre-fed ad libitum (AL) or 40% DER die t for 8-10 weeks, The kinase activities in mouse epidermis were determined by immune complex kinase assays at 0.5, 1, 4, or 6 h following treatment wi th 3.2 nmol TPA to the shaved dorsal backs. ERK activity at 1 h post-TPA tr eatment was nearly 5-fold (P < 0.005) above basal levels in AL mice while t he increase was abolished in DER mice, The TPA-induced ERK activity in AL m ice was accompanied by increased phosphorylation of ERK1 and ERK2 (P < 0.05 ), which was abrogated in DER mice. In addition, DER mice exhibited reduced expression of total ERK1 and ERK2 and higher proportions of ERK1 and ERK2 phosphorylation in comparison with AL mice (P < 0.05), JNK activity was dec reased at 1 and 6 h but increased at 4 h (P < 0.05) post-TPA treatment. TPA did not change p38 kinase activity at the time points tested, Neither JNK nor p38 activity was altered by DER, Taken together, our results indicated for the first time that DER blocked the TPA stimulation of ERK activity and suggested that the inhibition of TPA-induced AP-1 activity by DER is likel y through inhibition of ERK but not JNK or p38 kinase pathway.