5-Aminoimidazole-4-carboxyamide-1-{beta}-D-ribofranoside stimulates the rat enhancer of split- and hairy-related protein-2 gene via atypical protein kinase C lambda

In this study, we examined an issue of whether the SHARP-2 gene expression is regulated by AICAR via the AMPK. AICAR increased the level of SHARP-2 mRNA in H4IIE cells. Whereas an AMPK inhibitor, compound-C, had no effects on the AICAR-induction, inhibitors for both phosphoinositide 3-kinase (PI 3-K) and protein kinase C (PKC) completely diminished the effects of AICAR. Western blot analyses showed that AICAR rapidly activated atypical PKC lambda (aPKC). In addition, when a dominant negative form of aPKC was expressed, the induction of SHARP-2 mRNA level by AICAR was inhibited. Calcium ion is not required for the activation of aPKC. A calcium ion-chelating reagent had no effects on the AICAR-induction. Furthermore, the AICAR-induction was inhibited by treatment with an RNA polymerase inhibitor or a protein synthesis inhibitor. Thus, we conclude that the AICAR-induction of the SHARP-2 gene is mediated at transcription level by a PI 3-K/aPKC pathway.

Source: Journal of Biochemistry - March 20, 2016 Category: Biochemistry Authors: Komatsu, Y., Yanagisawa, Y., Moriizumi, M., Tsuchiya, Y., Yokouchi, H., Otsuka, H., Aoyagi, M., Tsukada, A., Kanai, Y., Haneishi, A., Takagi, K., Asano, K., Ono, M., Tanaka, T., Tomita, K., Yamada, K. Tags: Regular Papers Source Type: research