The Interaction of Osmotic and Heavy Metal Stress in C. elegans

Abstract

Most cells encounter some form of cellular stress (e.g., hypoxia, unfolded proteins, oxidative stress) during their life cycle. To combat such stresses, cells activate a variety of response pathways that can ameliorate the effects of the stress. Relatively little is understood about how these pathways interact when cells are challenged with multiple stresses simultaneously. Our goal is to understand how multiple forms of concurrent stress can alter cellular response pathways, and the subsequent impact on health and survival. We examined the combination of heavy metal and osmotic stress, induced by cadmium chloride and sodium chloride, respectively, in C. elegans. We found that lifespan is decreased by the combined stress to a greater extent than either individual stress and identified a potential mechanism for this increased toxicity. Cadmium disrupts the osmotic stress response by interfering with the production of glycerol, an osmolyte that is typically upregulated as a core part of the osmotic stress response in C. elegans. In addition, we have evidence supporting both antagonistic and synergistic models of interaction between cadmium and sodium stress. Based on our work and the literature surrounding cadmium and sodium stress response, we have identified multiple points at which the two response pathways may interact. In future work we will evaluate each mechanism and determine which are critical to the downstream consequences of the combined stress and associated stress response.