TRP Channels as Cellular Targets of Particulate Matter

Abstract

Particulate matter (PM) is constituted by particles with sizes in the nanometer to micrometer scales. PM can be generated from natural sources such as sandstorms and wildfires, and from human activities, including combustion of fuels, manufacturing and construction or specially engineered for applications in biotechnology, food industry, cosmetics, electronics, etc. Due to their small size PM can penetrate biological tissues, interact with cellular components and induce noxious effects such as disruptions of the cytoskeleton and membranes and the generation of reactive oxygen species. Here, we provide an overview on the actions of PM on transient receptor potential (TRP) proteins, a superfamily of cation-permeable channels with crucial roles in cell signaling. Their expression in epithelial cells and sensory innervation and their high sensitivity to chemical, thermal and mechanical stimuli makes TRP channels prime targets in the major entry routes of noxious PM, which may result in respiratory, metabolic and cardiovascular disorders. On the other hand, the interactions between TRP channel and engineered nanoparticles may be used for targeted drug delivery. We emphasize in that much further research is required to fully characterize the mechanisms underlying PM-TRP channel interactions and their relevance for PM toxicology and biomedical applications.

Airway Exposure to Polyethyleneimine Nanoparticles Induces Type 2 Immunity by a Mechanism Involving Oxidative Stress and ATP Release

“…The exact mechanism by which PEI activates TRPV1 receptors is presently unclear. Previous studies with silica nanoparticles (SiNPs) have suggested that cell surface perturbations resulting from SiNP particles striking the plasma membrane can produce TRPV1 activation by mechanical stimulation [54]. In contrast, insoluble electrophilic compounds present in coal fly ash particles activate TRPV1 through interactions with amino acids within the pore-loop region of the channel [55].…”

“…In contrast, insoluble electrophilic compounds present in coal fly ash particles activate TRPV1 through interactions with amino acids within the pore-loop region of the channel [55]. Diesel exhaust particles can also open TRPV1 channels in epithelial cells by indirectly activating protease-activated receptor 2 (PAR2), resulting in Ca 2+ mobilization from internal stores, inflammatory mediator release and matrix metalloprotease activation [54]. Increasing extracellular concentrations of Na + , Mg 2+ , and Ca 2+ also opens TRPV1 channels expressed in HEK293 cells and oocytes presumably by interacting with two glutamate residues (E600 and E648) located near the pore region of the channel [56].…”

A Real-Time Comparison of Four Particulate Matter Size Fractions in the Personal Breathing Zone of Paris Subway Workers: A Six-Week Prospective Study

“…Epidemiological and toxicological studies show varying types and degrees of health effects related to PM, suggesting a role for both the chemical composition (such as transition metals and combustion-derived primary and secondary organic particles) and physical properties (size, shape, and surface area) along with concentration [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Yet, the research in this field is limited and controversial, particularly when comparing the results from epidemiological and experimental (in vivo and in vitro) studies [ 18 ].…”

Silica Nanoparticles Inhibit ATP Responses of Human Airway Epithelial 16HBE Cells

“…On the other hand, recent research has illustrated the importance of studying also the acute interaction of NPs with specific cellular structures and signaling pathways. For instance, NP-induced modulation in the time scales of seconds and minutes have been reported for cation-permeable channels that play crucial roles in cell signaling [30][37] [39][41] [42]. In this sense, ATP-mediated signaling is considered to be involved in inflammatory responses to NPs in multiple cell types [43][44][45][46][47] [48].…”