更新于：2024-11-01

YAP1 x MnSOD

更新于：2024-11-01

基本信息

关联

项与 YAP1 x MnSOD 相关的药物

RFX5-AS1

靶点

MnSOD x YAP1

作用机制

MnSOD inhibitors [+1]

在研机构

University of Sultan Qaboos

原研机构

University of Sultan Qaboos

在研适应症

卵巢癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 YAP1 x MnSOD 相关的临床结果

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100 项与 YAP1 x MnSOD 相关的转化医学

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0 项与 YAP1 x MnSOD 相关的专利（医药）

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项与 YAP1 x MnSOD 相关的文献（医药）

2024-07-01·Cellular Signalling

Inhibition of YAP/TAZ pathway contributes to the cytotoxicity of silibinin in MCF-7 and MDA-MB-231 human breast cancer cells

Article

作者: Zhao, Haina ; Mizuno, Kazunori ; Zhao, Ruxiao ; Liu, Weiwei ; Ikejima, Takashi ; Fujisaki, Hitomi ; Fu, Jianing ; Liu, Siyu ; Xiang, Yinlanqi ; Hattori, Shunji ; Hayashi, Toshihiko

Breast cancer is one of the most common cancers threatening women's health. Our previous study found that silibinin induced the death of MCF-7 and MDA-MB-231 human breast cancer cells. We noticed that silibinin-induced cell damage was accompanied by morphological changes, including the increased cell aspect ratio (cell length/width) and decreased cell area. Besides, the cytoskeleton is also destroyed in cells treated with silibinin. YAP/TAZ, a mechanical signal sensor interacted with extracellular pressure, cell adhesion area and cytoskeleton, is also closely associated with cell survival, proliferation and migration. Thus, the involvement of YAP/TAZ in the cytotoxicity of silibinin in breast cancer cells has attracted our interests. Excitingly, we find that silibinin inhibits the nuclear translocation of YAP/TAZ in MCF-7 and MDA-MB-231 cells, and reduces the mRNA expressions of YAP/TAZ target genes, ACVR1, MnSOD and ANKRD. More importantly, expression of YAP1 gene is negatively correlated with the survival of the patients with breast cancers. Molecular docking analysis reveals high probabilities for binding of silibinin to the proteins in the YAP pathways. DARTS and CETSA results confirm the binding abilities of silibinin to YAP and LATS. Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAP^S127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies.

2024-06-01·Journal of Assisted Reproduction and Genetics

Mechanisms of YAP1-mediated trophoblast ferroptosis in recurrent pregnancy loss

Article

作者: Liu, Hua ; Dai, Fangfang ; Chen, Jing ; Li, Zhidian ; Cheng, Yanxiang ; Chen, Liping ; Huang, Yanjie

PURPOSEThe purpose of our study is to investigate the function of YAP1 in the trophoblast ferroptosis and maternal-fetal interface communication of RPL.METHODSWe collected 25 villous tissues and detected the expression of YAP1. Cell counting kit-8 assay, scratch wound-healing assay, and Matrigel invasion assay were performed to observe the proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Subsequently, measured the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), SLC7A11, SOD2, and GPX4. Ultimately, the use of ferroptosis activator (erastin) and inhibitor (Ferrostatin-1, fer-1) further confirmed the regulation by YAP1. In addition, established an in vitro-induced cell model to study the effect of YAP1 on the decidualization process. Finally, animal models were implemented for further confirmation.RESULTSWe found that YAP1 was downregulated in RPL patients. Overexpression of YAP1 could significantly enhance the proliferation, migration, and invasion of trophoblasts, and inhibit ferroptosis. Knocking down YAP1 exhibited the opposite effect. Rescue experiments have shown that YAP1 could upregulate the expression of SLC7A11 and GPX4, which are key molecules in the classic pathway of ferroptosis. In addition, the decidualization was impaired when hESCs were treated with conditioned medium of YAP1 knockdown trophoblasts. Moreover, we found that Yap1, Slc7a11, and Gpx4 were downregulated in the RPL mice, along with increased MDA and decreased GSH.CONCLUSIONDownregulation of YAP1 induces ferroptosis, thereby damaging the trophoblast invasion processes, which also disturbs the communication at the maternal-fetal interface. Our study identified YAP1 as a potential key molecule in the pathogenesis of RPL.

2023-02-01·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Two faces of TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl) – An antioxidant or a toxin?

Article

作者: Stępień, Karolina ; Szlachcikowska, Dominika ; Galiniak, Sabina ; Kielar, Patrycja ; Mołoń, Mateusz

2,2,6,6-Tetramethylpiperidine-1-oxyl, commonly known as TEMPO, is one of the compounds called nitroxides that are used in the chemical industry for synthesis of many organic compounds as well as for electrodes in all-organic radical batteries. Additionally, TEMPO is a widely used antioxidant in scientific studies. Technological progress and simultaneous care for the environment leads to resorting to new industrial methods which require the use of compounds that have not been fully tested for their impact on living organisms. Therefore, TEMPO may be an environmental pollutant and its effect on living organisms is not fully understood. The aim of our study was to determine the influence of TEMPO on the physiology, chronological lifespan and wide transcription changes of a eukaryotic model organism, namely the Saccharomyces cerevisiae yeast. For this purpose, we used the BY4741 wild-type and isogenic mutants with a disorder in the response to oxidative stress (sod1Δ, sod2Δ, yap1Δ) and repair of DNA damage (rad52Δ). We showed that supplementation with TEMPO inhibited the cell growth rate of all analyzed strains while simultaneously slowing down the aging of post-mitotic cells in the yeast population. In addition, TEMPO-treated yeast cells manifested a significantly increased level of metabolism in the wild-type and sod2Δ strains. TEMPO also displayed genoprotective effect by reducing the number of DNA double-strand breaks in cells. Here, we are the first to show the widespread effect of TEMPO on yeast. In conclusion, we have shown that, contrary to the commonly accepted notion, TEMPO has also a toxic effect, especially on active mitotic cells. We hypothesize that translation impairment or ribosome biogenesis disorder is likely to be considered secondary effects of TEMPO toxicity related to cell cycle arrest. Therefore, despite the growing interest in the use of this compound in the chemical industry, its toxic effect on the environment, especially biosphere, should be taken into account.