Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma.
Cassandra E Deering-RiceChris StockmannErin G RomeroZhenyu LuDarien ShapiroBryan L StoneBernhard FasslFlory NkoyDerek A UchidaRobert M WardJohn M VeranthChristopher A ReillyPublished in: The Journal of biological chemistry (2016)
Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control.
Keyphrases
- poor prognosis
- binding protein
- chronic obstructive pulmonary disease
- neuropathic pain
- lung function
- particulate matter
- municipal solid waste
- induced apoptosis
- heavy metals
- allergic rhinitis
- cerebral ischemia
- sewage sludge
- endothelial cells
- copy number
- gene expression
- air pollution
- cell death
- magnetic resonance
- cancer therapy
- long non coding rna
- early onset
- spinal cord
- single cell
- drug delivery
- spinal cord injury
- diabetic rats
- cell therapy
- single molecule
- replacement therapy
- smoking cessation
- dna methylation
- pi k akt
- water soluble
- induced pluripotent stem cells
- contrast enhanced
- genome wide