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Yoda1‐induced phosphorylation of the Akt and ERK1/2 does not require Piezo1 activation
Author(s) -
Paz Nathaniel G.,
Frangos John A.
Publication year - 2018
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.2018.32.1_supplement.581.5
Subject(s) - piezo1 , mechanosensitive channels , protein kinase b , phosphorylation , microbiology and biotechnology , chemistry , calcium in biology , calcium , calcium channel , agonist , signal transduction , intracellular , mechanotransduction , biophysics , voltage dependent calcium channel , ion channel , biology , biochemistry , receptor , organic chemistry
Piezo1 is a mechanosensitive cation channel that is expressed by endothelial cells (ECs) and can be activated by fluid shear stress. It has been previously shown to be important for a number of shear‐induced EC responses, ranging from increased intracellular calcium to cell alignment. Most recently, Piezo1 has been implicated as a critical regulator of vascular tone and blood pressure. Yoda1, a selective small molecule agonist of Piezo1, has been shown to induce responses similar to those activated by fluid shear stress in ECs, such as calcium influx. Since shear stress‐induced intracellular calcium release is known to cause activation of Akt and ERK1/2, we sought to determine whether Yoda1 stimulation of EC can lead to similar responses and whether they are Piezo1‐mediated. In this study, we show that Yoda1 can robustly activate both the Akt and ERK1/2 signaling pathways in ECs. Additionally, we found that the ion channel antagonists, gadolinium and ruthenium red, but not the specific Piezo‐blocking peptide, GsMTx4, effectively blocks Yoda1‐induced Akt activation. Taken together, our results suggest that despite Yoda1 being a selective Piezo1 agonist, Yoda1‐induced activation of these two independent signaling pathways is not entirely dependent on Piezo1 activation. Support or Funding Information This work was supported by NIH MERIT Award R37 HL040696 to J.A.F. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .