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.

Maternal Caffeine Intake Disrupts Eggshell Integrity and Retards Larval Development by Reducing Yolk Production in a Caenorhabditis elegans Model

“…The physiological effects of caffeine intake in C. elegans are highly dose dependent [6]. Previous reports about the effects of caffeine using a C. elegans model indicate that the intake of a high dose of caffeine (>10 mM) showed adverse effects, such as developmental arrest, activation of stress-response pathways, and stimulation of food-avoidance behavior [6][7][8], whereas animals treated with a low dose of caffeine (<10 mM) generally showed beneficial effects such as lifespan extension, antioxidant effects, and protection of neurodegeneration [10,28,29]. However, the mechanism by which maternal caffeine intake affects not only the mother but also the offspring remains largely unknown.…”

Caffeine Protects Dopaminergic Neurons From Dopamine-Induced Neurodegeneration via Synergistic Adenosine-Dopamine D2-Like Receptor Interactions in Transgenic Caenorhabditis elegans

“…In some cases, caffeine may enhance rotational behavior as shown by the same author (Yu et al, 2006 ), which was said to contrast with the attenuation of L-DOPA-induced rotation upon deletion of A2A A R genes (Freduzzi et al, 2002 ). Instead of being paradoxical, this points out to the dose dependence of caffeine action, which was repeatedly shown to be beneficial at low doses and toxic at high doses (Bridi et al, 2015 ; Al-Amin et al, 2016 ). In the context of our proposed mechanism in C. elegans , therefore, a low-dose administration of caffeine (10 mM) could increase availability of DOP2Rs to dopamine and enhance the dopamine response, which would then modulate neuroprotection.…”

Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound

“…For example, robusta coffee contains 1.7–4.0% of caffeine, which is almost twice the content of Arabica coffee (0.8–1.4%) [ 9 , 10 , 11 , 12 ]. Caffeine is reported to cause side effects, such as insomnia, palpitations, an increase in the frequency of urination, headaches, and other symptoms—this is in addition to its main pharmacological effect as a stimulant [ 13 , 14 , 15 , 16 , 17 ].…”