更新于：2024-11-01

PLAAT

更新于：2024-11-01

基本信息

别名

HRAS like suppressor family、lecithin:retinol acyltransferase like、Phospholipase A/acyltransferase family

+ [1]

简介-

关联

项与 PLAAT 相关的药物

LEI-301

靶点

PLAAT

作用机制

PLAAT 抑制剂

在研机构

Academisch Ziekenhuis Leiden

原研机构

University of Leiden

在研适应症-

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 PLAAT 相关的临床结果

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100 项与 PLAAT 相关的转化医学

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0 项与 PLAAT 相关的专利（医药）

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2,105

项与 PLAAT 相关的文献（医药）

2024-11-01·Anti-Cancer Drugs

Interference with PLA2G16 promotes cell cycle arrest and apoptosis and inhibits the reprogramming of glucose metabolism in multiple myeloma cells by modulating the Hippo/YAP signaling pathway

Article

作者: Huang, Bo ; Li, Hongyan ; Mou, Xiaoyu ; Zhang, Yi ; Fan, Xiaoqiang

Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot. The transfection efficacy of sh-PLA2G16 and oe-YAP was examined using reverse transcription-quantitative PCR and western blot. Through cell counting kit-8 assay and 5-ethynyl-2′- deoxyuridine staining, multiple myeloma cell viability and proliferation were detected. Flow cytometry was used to measure cell apoptosis and cell cycle distribution. Oxygen consumption rate, the activities of mitochondrial respiratory chain complexes I–V, and the activity of caspase-3 were estimated with Seahorse XF24 analyzer, oxidative phosphorylation activity assay kit, and caspase-3 assay kit, respectively. Lactate production and glucose consumption were evaluated usingcorresponding assay kits. Western blot was employed to meaure proteins associated with cell cycle, glycolysis, pentose phosphate pathway as well as Hippo/YAP signaling pathway. In this study, PLA2G16 expression was greatly increased in multiple myeloma cells and PLA2G16 silence inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle arrest, and suppressed the reprogramming of glucose metabolism in multiple myeloma. It was also identified that PLA2G16 depletion inhibited the Hippo/YAP signaling pathway. Further experiments revealed that the overexpression of YAP partially reversed the inhibitory effects of PLA2G16 silence on multiple myeloma cell malignant development and the reprogramming of glucose metabolism. Collectively, PLA2G16 silence impeded multiple myeloma progression and inhibited glucose metabolism reprogramming by blocking the Hippo/YAP signaling pathway.

2024-11-01·Urologia Journal

Phospholipase A2 expression in prostate cancer as a biomarker of good prognosis: A comprehensive study in patients with long follow-up

Article

作者: Silva, Iran A ; Gattaz, Wagner F ; Nahas, Willian C ; Srougi, Miguel ; Guimarães, Vanessa R ; Leite, Katia R. M ; Mendes, Keith T ; Reis, Sabrina T ; Recuero, Saulo da Cunha ; Pimenta, Ruan C. P ; Viana, Nayara I ; Camargo, Juliana A ; Talib, Leda L

Background: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. Methods: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. Results: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. Conclusion: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival.

2024-10-01·Prostaglandins & Other Lipid Mediators

Plaat1l1 controls feeding induced NAPE biosynthesis and contributes to energy balance regulation in zebrafish

Article

作者: Dosoky, Noura S ; Yin, Linlin ; Chen, Wenbiao ; Mashhadi, Zahra ; Davies, Sean S

Dysregulation of energy balance leading to obesity is a significant risk factor for cardiometabolic diseases such as diabetes, non-alcoholic fatty liver disease and atherosclerosis. In rodents and several other vertebrates, feeding has been shown to induce a rapid rise in the intestinal levels of N-acyl-ethanolamines (NAEs) and the chronic consumption of a high fat diet abolishes this rise. Administering NAEs to rodents consuming a high fat diet reduces their adiposity, in part by reducing food intake and enhancing fat oxidation, so that feeding-induced intestinal NAE biosynthesis appears to be critical to appropriate regulation of energy balance. However, the contribution of feeding-induced intestinal NAE biosynthesis to appropriate energy balance remains poorly understood in part because there are multiple enzymes that can contribute to NAE biosynthesis and the specific enzyme(s) that are responsible for feeding-induced intestinal NAE biosynthesis have not been identified. The rate-limiting step in the intestinal biosynthesis of NAEs is formation of their immediate precursors, the N-acyl-phosphatidylethanolamines (NAPEs), by phosphatidylethanolamine N-acyltransferases (NATs). At least six NATs are found in humans and multiple homologs of these NATs are found in most vertebrate species. In recent years, the fecundity and small size of zebrafish (Danio rerio), as well as their similarities in feeding behavior and energy balance regulation with mammals, have led to their use to model key features of cardiometabolic disease. We therefore searched the Danio rerio genome to identify all NAT homologs and found two additional NAT homologs besides the previously reported plaat1, rarres3, and rarres3l, and used CRISPR/cas9 to delete these two NAT homologs (plaat1l1 and plaat1l2). While wild-type fish markedly increased their intestinal NAPE levels in response to a meal after fasting, this response was completely ablated in plaat1l1^-/-fish. Furthermore, plaat1l1^-/- fish fed a standard flake diet had increased weight gain and glucose intolerance compared to wild-type fish. The results support a critical role for feeding-induced NAPE and NAE biosynthesis in regulating energy balance and suggest that restoring this response in obese animals could potentially be used to treat obesity and cardiometabolic disease.

项与 PLAAT 相关的新闻（医药）

2022-10-04

·生物谷

一个月5天即可！最新研究表明模仿禁食饮食周期可以改善阿尔茨海默病

阿尔茨海默病是目前世界上几大致死疾病之一，其有着难以预防、难以治愈甚至是难以延缓进展的特点。而根据《中国阿尔茨海默病报告2021》的调查结果显示中国的AD的患病率和死亡率均略高于全球平均水平，且在女性中的相关数据高于男性。第93届奥斯卡金像奖最佳影片《困在时间里的父亲》就是一部讲述阿尔茨海默病患者的电影，这个电影以阿尔茨海默症病人为主视角，用影像再现了阿尔茨海默症患者脑海中那些彻底糊化的物质。《困在时间里的父亲》海报阿尔茨海默病(Alzheimer’s disease，AD)是一种神经退行性疾病，其特征是淀粉样β蛋白(amyloid-beta，Aβ)通过导致tau蛋白过度磷酸化和纤维缠结的形成的方式改变激酶和磷酸酶活性。这种独特的神经病理可导致炎症和氧化损伤、突触变性和神经元死亡，最终影响大脑皮层和海马区的学习、记忆功能。根据南加州大学伦纳德·戴维斯老年学学院领导的一项新研究，模仿禁食饮食周期似乎延缓了阿尔茨海默病小鼠的病理进展，改善其认知行为能力。doi: 10.1016/j.celrep.2022.111417大家或许会有疑问，什么是模仿禁食饮食呢？模仿禁食饮食（Fasting-mimicking diet，FMD）是一种低卡路里/低蛋白质但高不饱和脂肪的饮食，它对压力抵抗或长寿相关指标的影响类似于纯水禁食引起的影响，但它能最大限度地减少长期禁食的负担，因为它提供了营养物质和微量元素。在这个研究中，研究者喂给小鼠的FMD配方有两种，分为第1天饮食和第2~4/5天饮食。第1天饮食由大约55%的脂肪，36%的碳水化合物和9%的蛋白质组成，小鼠的摄入量在12.36kJ~17.31kJ之间。第2~4/5天饮食由大约43.3%的脂肪、47.4%的碳水化合物和9.3%的蛋白质组成，小鼠每天的摄入量在8.17kJ-11.44kJ之间。研究者选用的是3xTg和E4FAD两种转基因小鼠模型，3xTg的AD小鼠模型同时拥有 Aβ 和 tau蛋白的病理表现，这和人类阿尔茨海默症患者病理表现类似，而E4FAD小鼠模型可以表达人ApoE4基因亚型，ApoE4携带者对于阿尔茨海默症治疗的研究有重要意义。给予小鼠每月两次为期5天的模仿禁食饮食周期，对照组及FMD间歇期均按照啮齿类动物饮食标准进行喂食，几个周期后分别对两种模型的小鼠进行测试。经过基线行为测试（包括自发交替行为（SAB）和高架十字迷宫（EPM））以及Barnes迷宫测试发现，每月两次的FMD周期可以改善两种转基因小鼠模型的视觉注意力、工作记忆和空间记忆，同时可以改善焦虑行为，使其增加探索活动。Tig3.两种小鼠模型SAB评分情况在后续的病理研究中发现，经过FMD周期的两种小鼠模型降低了AD关键病理标志物的表达水平，包括Aβ和过度磷酸化的tau蛋白，以及小胶质细胞密度和神经炎症标志物，通过这些来改善小鼠认知功能。而其部分原因可能是通过调节小胶质细胞和巨噬细胞的活动，使其发挥保护功能，包括清除Aβ，同时减少毒性O2-/ONOO-的产生。Tig4.两种小鼠模型免疫反应主要代表图片研究还发现，与3xTg对照组相比，FMD组的3xTg小鼠皮质中Egr(1-4)基因的表达均有所下调。在哺乳动物中，Egr1的表达主要通过能量传感器AMPK上调，Egr1本身也会在低卡路里条件或被二甲双胍等药物激活。在神经系统中，Egr1的下调与炎症和病理表现的减少有关，通过siRNA或药物抑制Egr1的表达可能会减少小胶质细胞激活，并可能缓解AD造成的神经炎症。由此可见，模仿禁食的饮食周期可以有效改善AD小鼠的临床表现，延缓其病理进展。那么，FMD的饮食周期应用到人类患者身上是否安全有效呢？为了评估在确诊为轻度遗忘性认知障碍(amnestic mild cognitive impairment,aMCI)或轻度AD的患者中进行FMD周期的可行性和安全性，研究者们启动了一项I/II期随机对照(单盲)临床研究，测试了40名营养状况良好的aMCI或轻度AD患者每月FMD周期的效果。结果表明，在aMCI或轻度AD患者中，每月实施一次为期5天的FMD周期总体上是安全的。但这一结果仍需大型的临床研究和数据来支撑，仍需明确FMD周期是否真的可以延缓此类患者的认知衰退，推迟aMCI患者向AD的转化，同时影响相关生物标记物的表达。综上所述，模仿禁食饮食的饮食周期在营养状况良好的轻度遗忘性认知障碍或轻度阿尔茨海默症患者身上应用或许是安全的，而这种饮食周期可以改善患者认知功能，延缓病情进展。在未来，这或许可以成为临床上该类患者治疗的一个新方向。参考文献：1.中国阿尔茨海默病报告20212.Rangan, Priya et al. “Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.” Cell reports vol. 40,13 (2022): 111417. doi:10.1016/j.celrep.2022.111417撰稿｜一根羊毛编辑｜小耳朵

siRNA