Dataset Information

Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation.

ABSTRACT: Piezo1 is a mechanosensitive cation channel that is activated by shear stress in endothelial cells (ECs). It has been shown to mediate shear-induced EC responses, including increased calcium influx, and vascular functions, such as vascular tone and blood pressure. Yoda1, a selective Piezo1 activator, has been shown to mimic shear-induced responses in ECs. Since shear-induced calcium influx causes Akt and ERK1/2 activation in ECs, we examined the effects of Yoda1 and the role of Piezo1 on their activation. Here, we show that Yoda1 robustly activates Akt and ERK1/2 in ECs. Additionally, the Piezo1 antagonists, gadolinium and ruthenium red, but not GsMTx4, effectively blocks Yoda1-induced Akt activation. Our results suggest that Yoda1-induced Akt and ERK1/2 activation is not dependent on Piezo1.

SUBMITTER: Dela Paz NG

PROVIDER: S-EPMC5835220 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation.

Dela Paz Nathaniel G NG Frangos John A JA

Biochemical and biophysical research communications 20180208 1

Piezo1 is a mechanosensitive cation channel that is activated by shear stress in endothelial cells (ECs). It has been shown to mediate shear-induced EC responses, including increased calcium influx, and vascular functions, such as vascular tone and blood pressure. Yoda1, a selective Piezo1 activator, has been shown to mimic shear-induced responses in ECs. Since shear-induced calcium influx causes Akt and ERK1/2 activation in ECs, we examined the effects of Yoda1 and the role of Piezo1 on their a ...[more]

PMID: 29428723

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Project description:Formononetin (FMNT) is a major bioactive compound from Astragalus membranaceus (Fisch.) Bunge, and has been widely used to treat conditions related to vascular insufficiency. However, the molecular mechanism for the therapeutic effect has not been well defined. This study aimed to investigate the effect and mechanism of FMNT on endothelial function. The potential targets and signaling pathways of FMNT in the setting of ischemia were predicted using network pharmacology analysis. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro studies and C57BL/6 mice were used for in vivo experiments. The results of the network pharmacology analysis showed that multiple signaling molecules including MAPK and PI3K-Akt pathways could be involved in the pharmacological actions of FMNT against ischemic diseases. The experimental validation data showed that FMNT significantly promoted the growth, proliferation, migration and tube formation of HUVECs in association with activation of endothelial nitric oxide synthase (eNOS) and promotion of intracellular nitric oxide (NO) production. FMNT also markedly activated Erk1/2 and Akt signaling in HUVECs. The enhanced endothelial function by FMNT was abolished when the cells were pre-treated with eNOS inhibitor. FMNT-induced eNOS/NO activation, endothelial function and angiogenesis was also effectively attenuated when Erk1/2 or Akt signaling pathway was inhibited. In addition, FMNT significantly promoted wound healing in C57BL/6 mice associated with activation of Erk1/2 and Akt signaling. Enhanced wound healing by FMNT in mice was prevented when eNOS-, Erk1/2, or Akt-medicated signaling was inhibited. Moreover, when Akt signaling was inhibited in HUVECs, FMNT was still able to activate Erk1/2 signaling without promotion of endothelial function. Similarly, FMNT could activate Akt signaling with no change in endothelial function when Erk1/2 signaling was attenuated in HUVECs. Conclusively, the present study demonstrated that FMNT significantly enhanced endothelial function and promoted angiogenesis in vitro and in vivo through activating Erk1/2- and Akt-mediated eNOS/NO signaling pathway. The data also suggested that simultaneous activation of Erk1/2 and Akt signaling was required for FMNT-induced promotion of endothelial function. Results from the present study might provide support and evidence for the application of FMNT during the clinical treatment of conditions related to vascular insufficiency.

Dataset Information

Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation.

Publications

Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation.

Similar Datasets

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