title: Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans.
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.
authors.affiliation: Department of Bioscience and Biotechnology and Institute of KU Bio-technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Amin
authors.affiliation: Department of Bioscience and Biotechnology and Institute of KU Bio-technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawasaki
authors.affiliation: Department of Bioscience and Biotechnology and Institute of KU Bio-technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Joomi
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Bioscience and Biotechnology and Institute of KU Bio-technology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Yhong-Hee
authors.initials: YH
authors.lastname: Shim
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; C502196:Hsp-4 protein, C elegans; D034741:RNA, Small Interfering; C526743:hsp-16.1 protein, C elegans; D002110:Caffeine
keywords: C. elegans development; caffeine; food-avoidance behavior; heat shock protein; proteomic analysis