Yoda1 is an agonist for both human and mouse Piezo1. Yoda 1 activates purified Piezo1 channels。The EC50 of mouse was 17.1 μm, and that of human was 26.6 μm[1].Yoda1 has been widely used to study the gating mechanism of Piezo and various PIEzO-related biological processes[5].
Yoda1 induces activation of both Akt and ERK1/2 in endothelial cells (ECs), which is not dependent on Piezo1[2].Yoda1 induced the activation of Akt and ERK1/2, and the increase of their respective phosphorylation levels reflected that the phosphorylation of the two signaling molecules also increased with the increase of Yoda1 concentration[4].Activation of Piezo1 by Yoda1, a Piezo1 agonist, caused calcium influx and profibrotic responses in HK2 cells and induced calcium-dependent protease calpain2 activation, followed by adhesion complex protein talin1 cleavage and upregulation of integrin β1. Also, Yoda1 promoted the link between ECM and integrin β1[7].Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration[8].
Agonist Yoda1 effectively inhibited calcium influx caused by hypertension. Antithrombotic studies proved that the inhibition of Piezo1 effectively inhibited arterial thrombosis and reduced the infarct size of stroke in hypertensive mice[6].A Yoda1-like exercise pill has the ability to specifically target and enhance Piezo1 activity during exercise[3].
References:
[1]: Syeda R, Xu J, et,al. Chemical activation of the mechanotransduction channel Piezo1. Elife. 2015 May 22;4:e07369. doi: 10.7554/eLife.07369. PMID: 26001275; PMCID: PMC4456433.
[2]:Dela Paz NG, Frangos JA. Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation. Biochem Biophys Res Commun. 2018 Feb 26;497(1):220-225. doi: 10.1016/j.bbrc.2018.02.058. Epub 2018 Feb 8. PMID: 29428723; PMCID: PMC5835220.
[3]:Beech DJ. Endothelial Piezo1 channels as sensors of exercise. J Physiol. 2018 Mar 15;596(6):979-984. doi: 10.1113/JP274396. Epub 2018 Jan 9. PMID: 29194632; PMCID: PMC5851887.
[4]: Kuriyama M, Hirose H, et,al. Piezo1 activation using Yoda1 inhibits macropinocytosis in A431 human epidermoid carcinoma cells. Sci Rep. 2022 Apr 15;12(1):6322. doi: 10.1038/s41598-022-10153-8. Erratum in: Sci Rep. 2022 May 12;12(1):7873. PMID: 35428847; PMCID: PMC9012786.
[5]: Douguet D, Patel A, et,al. Piezo Ion Channels in Cardiovascular Mechanobiology. Trends Pharmacol Sci. 2019 Dec;40(12):956-970. doi: 10.1016/j.tips.2019.10.002. Epub 2019 Nov 5. PMID: 31704174.
[6]: Zhao W, Wei Z, et,al.Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension. J Thromb Haemost. 2021 Dec;19(12):3113-3125. doi: 10.1111/jth.15504. Epub 2021 Oct 8. PMID: 34411418.
[7]: Zhao X, Kong Y, et,al. Mechanosensitive Piezo1 channels mediate renal fibrosis. JCI Insight. 2022 Apr 8;7(7):e152330. doi: 10.1172/jci.insight.152330. PMID: 35230979; PMCID: PMC9057604.
[8]: Lin CY, Song X, et,al. Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration. Cancers (Basel). 2022 Jul 13;14(14):3395. doi: 10.3390/cancers14143395. PMID: 35884459; PMCID: PMC9324638.
Yoda1 是人和小鼠 Piezo1 的激动剂。 Yoda 1激活纯化的Piezo1通道。小鼠EC50为17.1 μm，人为26.6 μm[1]。Yoda1已被广泛用于研究Piezo的门控机制和各种PIEzO相关生物过程[5].
Yoda1 诱导内皮细胞 (EC) 中 Akt 和 ERK1/2 的激活，这不依赖于 Piezo1[2]。Yoda1 诱导 Akt 和 ERK1/2 的激活，并且它们各自磷酸化水平的增加反映了两种信号分子的磷酸化也随着 Yoda1 浓度的增加而增加[4]。Yoda1 激活 Piezo1，一种 Piezo1 激动剂，导致钙流入和促纤维化反应在 HK2 细胞中诱导钙依赖性蛋白酶钙蛋白酶 2 激活，然后是粘附复合蛋白 talin1 裂解和整合素 β1 的上调。此外，Yoda1 还促进了 ECM 与整合素 β1[7] 之间的联系。Yoda1 增强了骨细胞的低幅度高频振动以调节 MDA-MB-231 乳腺癌细胞迁移[8 ].
激动剂 Yoda1 可有效抑制高血压引起的钙内流。抗血栓研究证明，抑制 Piezo1 可有效抑制高血压小鼠的动脉血栓形成并减少卒中的梗死面积[6]。练习[3]。