Azad Gajendra Kumar, Singh Vikash, Thakare Mayur Jankiram, Baranwal Shivani, Tomar Raghuvir Singh
Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, 462023, India.
Current address: Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
BMC Microbiol. 2014 Dec 19;14:317. doi: 10.1186/s12866-014-0317-0.
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 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.
Here, 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.
Our 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.
姜黄素(CUR)是一种从姜黄香料中提取的活性多酚,在古印度医学中已有数百年的传统应用历史,用于治疗多种疾病。CUR的生理效应已被证明具有多样性;然而,CUR所影响的靶分子和信号通路尚未得到充分描述。
在此,我们首次证明出芽酵母丝裂原活化蛋白激酶(MAPK)Hog1对于对CUR的反应至关重要。此外,通过向生长培养基中补充铁可挽救CUR诱导的Hog1磷酸化。用CUR处理后,Hog1迅速被磷酸化,但与对高渗休克(0.8 M NaCl)的反应不同,它会在较长时间内保持激活状态。对HOG信号通路突变体的详细分析表明,Pbs2p、Ptc2p和Ssk2p是最佳CUR诱导的Hog1磷酸化所必需的。我们还观察到对CUR处理的Hog1依赖性转录反应,该反应涉及甘油-3-磷酸脱氢酶1(GPD1)的上调,GPD1是高渗应激反应所必需的一个因子。
我们目前的发现揭示了Hog1 MAPK在调节CUR诱导的转录反应中的作用。我们预计我们的发现将增进对CUR对酿酒酵母分子作用模式的理解。