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Direct Implications for Caveolin‐1 In TRPV1 Mediated NO production: Elucidating A Mechanism Of Vasoreactivity
Author(s) -
Fahmy Joseph N.,
Andrei Spencer,
DelloStritto Daniel J.,
Geldenhuys Werner,
Damron Derek S.,
Bratz Ian N.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.684.15
Subject(s) - trpv1 , enos , chemistry , capsaicin , caveolae , caveolin 1 , microbiology and biotechnology , nitric oxide , nitric oxide synthase type iii , signal transduction , biochemistry , transient receptor potential channel , receptor , biology , nitric oxide synthase , organic chemistry
Caveolin‐1 (Cav‐1), a scaffolding protein responsible for the formation of caveolae, is ubiquitously expressed and prominently in endothelial cells. Moreover, Cav‐1 is known to associate with several ion channels including various Kv and TRP subtypes. It is well established that when Cav‐1 and endothelial nitric oxide synthase (eNOS) are bound, Cav‐1 exerts an inhibitory effect on eNOS activity and thus decreases NO production until a Ca 2+ dependent signal untethers the proteins. Our lab and others have shown that TRPV1 regulates eNOS activity and NO production; specifically, via a calcium‐mediated AKT‐CaMKII‐AMPK signaling cascade. Therefore, we hypothesize that TRPV1, Cav‐1, and eNOS form a regulatory protein complex in endothelial cells responsible for the modulation of NO production. Examination of the TRPV1 amino acid sequence revealed 4 potential Cav‐1 binding motifs (where Ø represents any aromatic amino acid and X represents any amino acid): ØXXØXXXXØØ, ØXXØXXXØ, ØXXXØXXØ, and ØXXXØXØ. Computational modeling predicted an interaction between TRPV1 and Cav‐1. Confirmation of a direct TRPV1/Cav‐1 association was illustrated using Proximity Ligation Assay (PLA) in mouse coronary endothelial cells, which was increased following treatment with the TRPV1 agonist capsaicin. Furthermore, capsaicin treatment decreased the interaction between Cav‐1 and eNOS visualized with PLA, further defining the nature of this NO mediated cellular response. Similarly, NO production increased following capsaicin treatment. In conclusion, this is the first evidence of a direct interaction between TRPV1 and Cav‐1 and its implications in the regulation of NO production and vascular function.