Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 179, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2023.113980
Keywords
Antimicrobial; Calcium; Cetylpyridinium chloride; Quaternary ammonium compound; Degranulation; Endoplasmic reticulum; Inositol 1,4,~5-triphosphate; Cytoplasmic pH; Mast cell; Microtubule; Plasma membrane potential
Categories
Ask authors/readers for more resources
Cetylpyridinium chloride (CPC) inhibits mast cell function by suppressing degranulation with antigen dose-dependence and at non-cytotoxic concentrations. It achieves this by disrupting phosphatidylinositol 4,5-bisphosphate and inhibiting store-operated Ca2+ entry (SOCE). Furthermore, CPC also inhibits microtubule polymerization.
Cetylpyridinium chloride (CPC) is an antimicrobial used in numerous personal care and janitorial products and food for human consumption at millimolar concentrations. Minimal information exists on the eukaryotic toxicology of CPC. We have investigated the effects of CPC on signal transduction of the immune cell type mast cells. Here, we show that CPC inhibits the mast cell function degranulation with antigen dose-dependence and at non-cytotoxic doses similar to 1000-fold lower than concentrations in consumer products. Previously we showed that CPC disrupts phosphatidylinositol 4,5-bisphosphate, a signaling lipid critical for store-operated Ca2+ entry (SOCE), which mediates degranulation. Our results indicate that CPC inhibits antigen-stimulated SOCE: CPC restricts Ca2+ efflux from endoplasmic reticulum, reduces Ca2+ uptake into mitochondria, and dampens Ca2+ flow through plasma membrane channels. While inhibition of Ca2+ channel function can be caused by alteration of plasma membrane potential (PMP) and cytosolic pH, CPC does not affect PMP or pH. Inhibition of SOCE is known to depress microtubule polymerization, and here we show that CPC indeed dose-dependently shuts down formation of microtubule tracks. In vitro data reveal that CPC inhibition of microtubules is not due to direct CPC interference with tubulin. In summary, CPC is a signaling toxicant that targets Ca2+ mobilization.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available