抄録
Decrease in saliva causes serious problems in clinical dentistry. There have been previous reports on tissue injuries of parotid glands inducing a dedifferentiation signal that causes the loss of function of acinar cells. Since both inhibitors for Src family kinase(SFK)and p38 MAP kinase(p38 MAPK)suppressed the dedifferentiation, SFK-p38 MAPK pathway was considered essential for the signaling. Even though Src and Yes were expressed in the parotid glands, the increase in phosphorylation level was not detected for conserved tyrosine residue in the kinase domain of Src or Yes that promotes kinase activity, following tissue injuries. In this study, the kinase activities were assayed by using the specific substrate for SFK to examine whether the enhancement of kinase activity of SFK was eventuated by tissue injuries. As a result, the activity of the total SFK was elevated after the cellular damage and was sustained for 2 h. To determine the activated SFK member, the SFK activity was examined by immunoprecipitation method with specific antibodies against each SFK member. Elevation of kinase activities of both Src and Yes was detected after cell damages. The elevation ratio of Src activity was higher than Yes, suggesting that the contribution of Src in the dedifferentiation signaling is higher. Diphenyleneiodonium, an NADPH oxidase inhibitor, suppressed the activation of SFK and p38 MAPK, and the expression of claudin-4, a dedifferentiation marker. These results suggest that the activation of SFK is induced by oxidative stresses and is essential for p38 MAPK-mediated dedifferentiation signaling.
