BMC Microbiology | |
Mitogen-activated protein kinase Hog1 is activated in response to curcumin exposure in the budding yeast Saccharomyces cerevisiae | |
Raghuvir Singh Tomar1  Shivani Baranwal1  Mayur Jankiram Thakare1  Vikash Singh1  Gajendra Kumar Azad2  | |
[1] 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 | |
关键词: Mitogen-activated protein kinases; Glycerol-3-phosphate dehydrogenase 1 (GPD1); Hog1 phosphorylation; HOG pathway; Curcumin; Yeast drug response; | |
Others : 1090573 DOI : 10.1186/s12866-014-0317-0 |
|
received in 2014-07-29, accepted in 2014-12-05, 发布年份 2014 | |
【 摘 要 】
Background
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.
Results
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.
Conclusions
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.
【 授权许可】
2014 Azad et al.; licensee BioMed Central.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150128161810958.pdf | 2895KB | download | |
Figure 6. | 64KB | Image | download |
Figure 5. | 38KB | Image | download |
Figure 4. | 61KB | Image | download |
Figure 3. | 109KB | Image | download |
Figure 2. | 34KB | Image | download |
Figure 1. | 73KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
【 参考文献 】
- [1]O’Rourke SM, Herskowitz I, O’Shea EK: Yeast go the whole HOG for the hyperosmotic response. Trends Genet 2002, 18(8):405-412.
- [2]Winkler A, Arkind C, Mattison CP, Burkholder A, Knoche K, Ota I: Heat stress activates the yeast high-osmolarity glycerol mitogen-activated protein kinase pathway, and protein tyrosine phosphatases are essential under heat stress. Eukaryot Cell 2002, 1(2):163-173.
- [3]Lawrence CL, Botting CH, Antrobus R, Coote PJ: Evidence of a new role for the high-osmolarity glycerol mitogen-activated protein kinase pathway in yeast: regulating adaptation to citric acid stress. Mol Cell Biol 2004, 24(8):3307-3323.
- [4]Panadero J, Pallotti C, Rodriguez-Vargas S, Randez-Gil F, Prieto JA: A downshift in temperature activates the high osmolarity glycerol (HOG) pathway, which determines freeze tolerance in Saccharomyces cerevisiae. J Biol Chem 2006, 281(8):4638-4645.
- [5]Aguilera J, Rodriguez-Vargas S, Prieto JA: The HOG MAP kinase pathway is required for the induction of methylglyoxal-responsive genes and determines methylglyoxal resistance in Saccharomyces cerevisiae. Mol Microbiol 2005, 56(1):228-239.
- [6]Marques JM, Rodrigues RJ, de Magalhaes-Sant’Ana AC, Goncalves T: Saccharomyces cerevisiae Hog1 protein phosphorylation upon exposure to bacterial endotoxin. J Biol Chem 2006, 281(34):24687-24694.
- [7]Garcia-Rodriguez LJ, Duran A, Roncero C: Calcofluor antifungal action depends on chitin and a functional high-osmolarity glycerol response (HOG) pathway: evidence for a physiological role of the Saccharomyces cerevisiae HOG pathway under noninducing conditions. J Bacteriol 2000, 182(9):2428-2437.
- [8]Reynolds TB, Hopkins BD, Lyons MR, Graham TR: The high osmolarity glycerol response (HOG) MAP kinase pathway controls localization of a yeast Golgi glycosyltransferase. J Cell Biol 1998, 143(4):935-946.
- [9]Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK: Turmeric and curcumin: biological actions and medicinal applications. Curr Sci India 2004, 87(1):44-53.
- [10]Jurenka JS: Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 2009, 14(2):141-153.
- [11]Aggarwal BB, Sundaram C, Malani N, Ichikawa H: Curcumin: the Indian solid gold. Adv Exp Med Biol 2007, 595:1-75.
- [12]Gupta SC, Kismali G, Aggarwal BB: Curcumin, a component of turmeric: from farm to pharmacy. Biofactors 2013, 39(1):2-13.
- [13]Shehzad A, Lee J, Lee YS: Curcumin in various cancers. Biofactors 2013, 39(1):56-68.
- [14]Monroy A, Lithgow GJ, Alavez S: Curcumin and neurodegenerative diseases. Biofactors 2013, 39(1):122-132.
- [15]Vera-Ramirez L, Perez-Lopez P, Varela-Lopez A, Ramirez-Tortosa M, Battino M, Quiles JL: Curcumin and liver disease. Biofactors 2013, 39(1):88-100.
- [16]Bahn YS: Master and commander in fungal pathogens: the two-component system and the HOG signaling pathway. Eukaryotic Cell 2008, 7(12):2017-2036.
- [17]Balkrishna SJ, Kumar S, Azad GK, Bhakuni BS, Panini P, Ahalawat N, Tomar RS, Detty MR: An ebselen like catalyst with enhanced GPx activity via a selenol intermediate. Org Biomol Chem 2014, 12(8):1215-1219.
- [18]Singh V, Azad GK, Mandal P, Reddy MA, Tomar RS: Anti-cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae. FEBS Lett 2014, 588(6):1044-1052.
- [19]Azad GK, Singh V, Mandal P, Singh P, Golla U, Baranwal S, Chauhan S, Tomar RS: Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity in Saccharomyces cerevisiae with inhibition of glutamate dehydrogenase being a target. FEBS Open Bio 2014, 4:77-89.
- [20]Golla U, Singh V, Azad GK, Singh P, Verma N, Mandal P, Chauhan S, Tomar RS: Sen1p contributes to genomic integrity by regulating expression of ribonucleotide reductase 1 (RNR1) in Saccharomyces cerevisiae. PLoS One 2013, 8(5):e64798.
- [21]Azad GK, Balkrishna SJ, Sathish N, Kumar S, Tomar RS: Multifunctional Ebselen drug functions through the activation of DNA damage response and alterations in nuclear proteins. Biochem Pharmacol 2012, 83(2):296-303.
- [22]Singh V, Azad GK, Reddy MA, Baranwal S, Tomar RS: Anti-cancer drug KP1019 induces Hog1 phosphorylation and protein ubiquitylation in Saccharomyces cerevisiae. Eur J Pharmacol 2014, 736:77-85.
- [23]Azad GK, Singh V, Tomar RS: Assessment of the biological pathways targeted by isocyanate using N-succinimidyl N-methylcarbamate in budding yeast Saccharomyces cerevisiae. PLoS One 2014, 9(3):e92993.
- [24]Baranwal S, Azad GK, Singh V, Tomar RS: Signaling of chloroquine-induced stress in the yeast Saccharomyces cerevisiae requires the Hog1 and Slt2 mitogen-activated protein kinase pathways. Antimicrob Agents Chemother 2014, 58(9):5552-5566.
- [25]Azad GK, Singh V, Golla U, Tomar RS: Depletion of cellular iron by curcumin leads to alteration in histone acetylation and degradation of Sml1p in Saccharomyces cerevisiae. PLoS One 2013, 8(3):e59003.
- [26]De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F: The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 2004, 427(6972):370-374.
- [27]Maeda T, Wurgler-Murphy SM, Saito H: A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 1994, 369(6477):242-245.
- [28]Tamas MJ, Rep M, Thevelein JM, Hohmann S: Stimulation of the yeast high osmolarity glycerol (HOG) pathway: evidence for a signal generated by a change in turgor rather than by water stress. FEBS Lett 2000, 472(1):159-165.
- [29]Hohmann S: Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 2002, 66(2):300-372.
- [30]Ferrigno P, Posas F, Koepp D, Saito H, Silver PA: Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J 1998, 17(19):5606-5614.
- [31]Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, Posas F: The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol Cell 2006, 23(2):241-250.
- [32]Albertyn J, Hohmann S, Thevelein JM, Prior BA: GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 1994, 14(6):4135-4144.
- [33]Brewster JL, de Valoir T, Dwyer ND, Winter E, Gustin MC: An osmosensing signal transduction pathway in yeast. Science 1993, 259(5102):1760-1763.
- [34]Alonso-Monge R, Navarro-Garcia F, Roman E, Negredo AI, Eisman B, Nombela C, Pla J: The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans. Eukaryotic Cell 2003, 2(2):351-361.
- [35]Sotelo J, Rodriguez-Gabriel MA: Mitogen-activated protein kinase Hog1 is essential for the response to arsenite in Saccharomyces cerevisiae. Eukaryotic Cell 2006, 5(10):1826-1830.
- [36]Minear S, O’Donnell AF, Ballew A, Giaever G, Nislow C, Stearns T, Cyert MS: Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation. Eukaryot Cell 2011, 10(11):1574-1581.
- [37]Posas F, WurglerMurphy SM, Maeda T, Witten EA, Thai TC, Saito H: Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 “two-component” osmosensor. Cell 1996, 86(6):865-875.
- [38]Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard CLSI Document M38-A2. Wayne: CLSI 2008, Clinical and Laboratory Standards Institute.
- [39]Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope W: EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST). Clin Microbiol Infect 2012, 18(7):E246-E247.
- [40]Albertyn J, Hohmann S, Thevelein JM, Prior BA: Gpd1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic-stress in Saccharomyces-Cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 1994, 14(6):4135-4144.
- [41]Pan W, Yang H, Cao C, Song X, Wallin B, Kivlin R, Lu S, Hu G, Di W, Wan Y: AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep 2008, 20(6):1553-1559.
- [42]Duan W, Yang Y, Yan J, Yu S, Liu J, Zhou J, Zhang J, Jin Z, Yi D: The effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the JAK2/STAT3 signaling pathway. Basic Res Cardiol 2012, 107(3):263.
- [43]Prasad CP, Rath G, Mathur S, Bhatnagar D, Ralhan R: Potent growth suppressive activity of curcumin in human breast cancer cells: modulation of Wnt/beta-catenin signaling. Chem Biol Interact 2009, 181(2):263-271.
- [44]Subramaniam D, Ponnurangam S, Ramamoorthy P, Standing D, Battafarano RJ, Anant S, Sharma P: Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One 2012, 7(2):e30590.
- [45]Squires MS, Hudson EA, Howells L, Sale S, Houghton CE, Jones JL, Fox LH, Dickens M, Prigent SA, Manson MM: Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol 2003, 65(3):361-376.