H89 (N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulphonamide) induces autophagy independently of protein kinase A inhibition

Hiroko Inoue*, Katsunori Hase, Arata Segawa, Tsuyoshi Takita


    研究成果: Article査読

    13 被引用数 (Scopus)


    Autophagy is a degradation pathway for cytoplasmic proteins and organelles in eukaryotes. Although the mechanisms of autophagy regulation are not completely understood, the target of rapamycin (TOR) signaling pathway plays a major role in controlling the induction of autophagy. Cyclic adenosine monophosphate (cAMP)/cAMP-dependent protein kinase A (PKA) has also been shown to regulate autophagy in yeast and mammalian cells. In an effort to elucidate the role of the cAMP/PKA pathway in autophagy, we used the PKA inhibitor N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulphonamide (H89) to treat mammalian cells. Our data demonstrated that H89 induced autophagy at 10 μM, which is a commonly used concentration for PKA inhibition, but PKA inhibition was not involved in the induction of autophagy. The effects of cAMP on autophagy seemed to be dependent on the cell type and the culture conditions. In addition, we investigated which protein kinase was involved in H89-induced autophagy because several kinases other than PKA have been shown to be inhibited by 10 μM of H89. There was no protein kinase largely responsible for autophagy induction, although the inhibition of Akt, which is a downstream effector protein kinase of phosphatidylinositol-3-kinase, appeared to be partially associated. Furthermore, H89-induced autophagy was independent of TOR. H89 is a widely used PKA inhibitor, but PKA-independent effects have been reported. Therefore, it is suggested that autophagy induction is a nonspecific effect of H89, and H89-induced autophagy is independent of the cAMP-PKA and the TOR pathways.

    ジャーナルEuropean Journal of Pharmacology
    出版ステータスPublished - 2013

    ASJC Scopus subject areas

    • 薬理学


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