Saccharomyces cerevisiae Hog1 MAP kinase pathway is activated in response to honokiol exposure.

Abstract

The goal of the study was to investigate the cellular tolerance mechanism in response to honokiol exposure. The broth microdilution method was employed to test the sensitivity of different Saccharomyces cerevisiae strains to honokiol. Intracellular levels of reactive oxygen species (ROSs) were determined by DCFH-DA staining. The phosphorylation of Hog1 was evaluated by Western blot analysis. The mRNA expressions of genes involved in the Ras-cyclic AMP (cAMP) pathway were analysed by real-time reverse transcription polymerase chain reaction. We found that the sod1▵ mutant was hypersensitive to honokiol and produced more ROS compared with wild-type and sod2▵ cells. Hog1 was phosphorylated in response to honokiol exposure and deletion of HOG1 increased the sensitivity to honokiol. The expressions of genes involved in the Ras-cAMP pathway were down-regulated after honokiol exposure; exogenous cAMP significantly reduced the phosphorylation of Hog1, although the level was higher than the control level. In addition to SOD1, the Ras-cAMP cascade and Hog1 MAP kinase pathway is essential for protecting against honokiol-induced oxidative stress. Our results provide insight into the understanding of the action mechanism of honokiol.