Browse > Article
http://dx.doi.org/10.14348/molcells.2016.2298

Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans  

Al-Amin, Mohammad (Department of Bioscience and Biotechnology and Institute of KU Biotechnology, Konkuk University)
Kawasaki, Ichiro (Department of Bioscience and Biotechnology and Institute of KU Biotechnology, Konkuk University)
Gong, Joomi (Department of Bioscience and Biotechnology and Institute of KU Biotechnology, Konkuk University)
Shim, Yhong-Hee (Department of Bioscience and Biotechnology and Institute of KU Biotechnology, Konkuk University)
Publication Information
Molecules and Cells / v.39, no.2, 2016 , pp. 163-168 More about this Journal
Abstract
Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.
Keywords
caffeine; C. elegans development; food-avoidance behavior; heat shock protein; proteomic analysis;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ekwall, B., Clemedson, C., Crafoord, B., Ekwall, B., Hallander, S., Walum, E., and Bondesson, I. (1998). MEIC evaluation of acute systemic toxicity. Part V. Rodent and human toxicity data for the 50 reference chemicals. Altern. Lab. Anim. 2, 571-616.
2 Haynes, C.M., and Ron, D. (2010). The mitochondrial UPR - protecting organelle protein homeostasis. J. Cell Sci. 123, 3849- 3855.   DOI
3 Kapulkin, W.J., Hiester, B.G., and Link, C.D. (2005). Compensatory regulation among ER chaperones in C. elegans. FEBS Lett. 579, 3063-3068.   DOI
4 Kawasaki, I., Jeong, M.H., Yun, Y.J., Shin, Y.K., and Shim, Y.H. (2013). Cholesterol-responsive metabolic proteins are required for larval development in Caenorhabditis elegans. Mol. Cells 36, 410-416.   DOI
5 Kuczkowski, K.M. (2009). Peripartum implications of caffeine intake in pregnancy: is there cause for concern? Rev. Esp. Anestesiol. Reanim. 56, 612-615.   DOI
6 Liu, Y., Samuel, B.S., Breen, P.C., and Ruvkun, G. (2014). Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508, 406-410.   DOI
7 Thompson KK, eds. Medication safety: a guide for health care facilities. (Bethesda, MD: American Society of Health-System Pharmacists), pp. 253-274.
8 Melo, J.A., and Ruvkun, G. (2012). Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Cell 149, 452-466.   DOI
9 Mesas, A.E., Leon-Muñoz, L.M., Rodriguez-Artalejo, F., and Lopez- Garcia, E. (2011). The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am. J. Clin. Nutr. 94, 1113-1126.   DOI
10 Min, H., Kawasaki, I., Gong, J., and Shim, Y.H. (2015). Caffeine induces high expression of cyp-35A family genes and inhibits the early larval development in Caenorhabditis elegans. Mol. Cells 38, 236-242.   DOI
11 Peltonen, J., Aarnio, V., Heikkinen, L., Lakso, M., and Wong, G. (2013). Chronic ethanol exposure increases cytochrome P-450 and decreases activated in blocked unfolded protein response gene family transcripts in Caenorhabditis elegans. J. Biochem. Mol. Toxicol. 27, 219-228.   DOI
12 Sutphin, G.L., Bishop, E., Yanos, M.E., Moller, R.M., and Kaeberlein, M. (2012). Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans. Longev. Healthspan. 1, 1:9.   DOI
13 Vilarim, M.M., Rocha Araujo, D.M., and Nardi, A.E. (2011). Caffeine challenge test and panic disorder: a systematic literature review. Expert. Rev. Neurother. 11, 1185-1195.   DOI
14 Weinberg, B.A., and Bealer, B.K. (2002). The caffeine advantage, ed. (NY, USA:The Free press).
15 Yoneda, T., Benedetti, C., Urano, F., Clark, S.G., Harding, H.P., and Ron, D. (2004). Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J. Cell Sci. 117, 4055-4066.   DOI
16 Ahn, D.H., Singaravelu, G., Lee, S., Ahnn, J., and Shim, Y.H. (2006). Functional and phenotypic relevance of differentially expressed proteins in calcineurin mutants of Caenorhabditis elegans. Proteomics 6, 1340-1350.   DOI
17 Benedetti, C., Haynes, C.M., Yang, Y., Harding, H.P., and Ron, D. (2006). Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response. Genetics 174, 229-239.   DOI
18 Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
19 Chen, L.W., Wu, Y., Neelakantan, N., Chong, M.F., Pan, A., and van Dam, R.M. (2014). Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis. BMC Med. 12, 174.   DOI