The Role of Ceramide Synthases Response to the Heavy Metal Cadmium Chloride

Abstract

Cadmium is an extremely toxic heavy metal that is hazardous to human health. In the United States, the primary source of cadmium exposure is in the food supply. Ingestion results in a buildup of cadmium in the body, specifically in the kidneys, which can lead to organ damage and cancer. This toxin has been known to induce stress in organisms by causing an accumulation of reactive oxidative species (ROS). To counter stress, cells respond with a variety of signaling pathways. We are interested in studying the sphingolipid pathway, which is known to mediate stress responses, but its role in defending against cadmium toxicity is unclear. We hypothesized that ceramide synthase, a sphingolipid metabolism enzyme, is required for survival to cadmium stress and decreased accumulation of ROS in animals. To test this, we utilized the model organism Caenorhabditis elegans. Ceramide synthase converts sphingosine to ceramide in the cells. We examined animals with mutations in ceramide synthase (hyl‐2 mutants) by treating worms to acute and chronic cadmium exposure and examining changes in survival, reproduction, and locomotion. We present data showing that cadmium does not affect animal reproduction, but it does affect survival upon exposure. Cadmium exposure resulted in decreased survival, however, and this result was less prominent in organisms possessing hyl‐2/ceramide synthase. We also found that the hyl‐2 gene is vital for oxidative stress response mechanisms. In addition, we present data on the effects of cadmium exposure on gene expression of sphingolipid metabolism enzymes using qPCR. These results are important because stress plays a role in aging, and if we better understand how stress is regulated via sphingolipids, it could become a potential pharmaceutical target to slow the degradative aging process.Support or Funding InformationNIH‐ 2R15AG052933