Mitogen-activated protein kinase Hog1 is activated in response to curcumin exposure in the budding yeast Saccharomyces cerevisiae.

Gajendra Kumar Azad,Mayur Jankiram Thakare,Vikash Singh,Shivani Baranwal,Raghuvir Singh Tomar

doi:10.1186/s12866-014-0317-0

Gajendra Kumar Azad, Mayur Jankiram Thakare + Show 3 more

Open Access

https://doi.org/10.1186/s12866-014-0317-0

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Abstract

BackgroundCurcumin (CUR), an active polyphenol derived from the spice turmeric, has been traditionally used for centuries in ancient Indian medicine to treat a number of diseases. The physiological effects of CUR have been shown to be diverse; however, the target molecules and pathways that CUR affects have yet to be fully described.ResultsHere, we demonstrate for the first time that the budding yeast mitogen-activated protein kinase (MAPK) Hog1 is essential for the response to CUR. Moreover, CUR-induced Hog1 phosphorylation was rescued by supplementation of iron to the growth medium. Hog1 was rapidly phosphorylated upon CUR treatment, but unlike the response to hyperosmotic shock (0.8 M NaCl), it remains activated for an extended period of time. A detailed analysis of HOG pathway mutants revealed that Pbs2p, Ptc2p, and Ssk2p are required for optimal CUR-induced Hog1 phosphorylation. We also observed a Hog1 dependent transcriptional response to CUR treatment that involved the up-regulation of glycerol-3-phosphate dehydrogenase 1 (GPD1), a factor that is essential for the hyperosmotic stress response.ConclusionsOur present finding revealed the role of Hog1 MAPK in regulation of CUR-induced transcriptional response. We anticipate that our finding will enhance the understanding on the molecular mode of action of CUR on S. cerevisiae.

Highlights

Curcumin (CUR), an active polyphenol derived from the spice turmeric, has been traditionally used for centuries in ancient Indian medicine to treat a number of diseases
The results from the FACS analysis revealed that the DMSO-treated cells quickly moved to the G2 phase within 30 minutes of release from the alpha-factor arrest (Figure 1A), whereas 50 μM CUR treatment led to a delay in the cell cycle progression (Figure 1B)
Even after 360 minutes, cells released into media containing 100 μM CUR were not able to progress to the G2 phase (Figure 1C), suggesting that CUR causes prolonged G1 phase leading to delay in cell cycle progression

Summary

Introduction

Curcumin (CUR), an active polyphenol derived from the spice turmeric, has been traditionally used for centuries in ancient Indian medicine to treat a number of diseases. The fundamental function of these MAPK pathways is to regulate gene expression in response to various extracellular signals. The HOG pathway involves the MAPK Hog that responds to increased extracellular osmolarity and is essential for cell survival under these conditions. Yeast cells respond to osmotic stress by activating Hog phosphorylation and, subsequently, translocating Hog to the nucleus where it directly interacts with several transcription factors to modulate gene expression. Evidence shows that the HOG pathway is essential for regulating the stress adaptation response induced by heat [2], citric acid [3], or low temperature [4]. The HOG pathway is involved in providing tolerance to methylglyoxal [5] and the bacterial endotoxin lipopolysaccharide (LPS) [6], and reportedly plays a role in cell wall maintenance [7] and the distribution of proteins within the Golgi [8]

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