更新于：2024-09-19

SOAT2

更新于：2024-09-19

基本信息

别名

ACACT2、ACAT-2、ACAT2

+ [4]

简介

Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol (PubMed:16647063, PubMed:11294643). Plays a role in lipoprotein assembly and dietary cholesterol absorption (PubMed:11294643). Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates (PubMed:11294643). May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa (PubMed:11294643). Has lower enzymatic activity compared to isoform 1. Has lower enzymatic activity compared to isoform 1.

关联

项与 SOAT2 相关的药物

Clonoamide

靶点

SOAT1 x SOAT2

作用机制

SOAT1抑制剂 [+1]

在研机构

Kitasato University [+1]

原研机构

Chugai Pharmaceutical Co., Ltd. [+1]

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

Pseudopyronine B

靶点

SOAT1 x SOAT2

作用机制

SOAT1抑制剂 [+1]

在研机构

Kitasato University

原研机构

Kitasato University

在研适应症

动脉粥样硬化

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

helvamide

靶点

SOAT1 x SOAT2

作用机制

SOAT1抑制剂 [+1]

在研机构

Kitasato University

原研机构

Kitasato University

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 SOAT2 相关的临床结果

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100 项与 SOAT2 相关的转化医学

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0 项与 SOAT2 相关的专利（医药）

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项与 SOAT2 相关的文献（医药）

2024-09-01·Phytomedicine

Investigating the potential mechanism and therapeutic effects of SLXG for cholesterol gallstone treatment

Article

作者: Wang, Wujie ; Zhou, Tong ; Li, Yuliang ; Liu, Bin ; Wang, Jiaxing ; Wang, Yang ; Chen, Zitong

BACKGROUNDShugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones.PURPOSEThis research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones.METHODSThe study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation.RESULTSThe study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism.CONCLUSIONSUsing systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

2024-08-01·Naunyn-Schmiedeberg's Archives of Pharmacology

Soat2 inhibitor avasimibe alleviates acute pancreatitis by suppressing acinar cell ferroptosis

Article

作者: Sun, Hui ; Pan, Jiajia ; Zhang, Siqin ; Xiao, Weiming ; Chen, Lin ; Luo, Weiwei ; Dong, Xiaowu ; Wang, Yaodong ; Lu, Guotao ; Xu, Hongwei

Ferroptosis, characterized by lipid peroxidation, plays a significant role in the pathogenesis of acute pancreatitis (AP). While sterol O-acyltransferase 2 (Soat2) is known for its crucial regulatory role in cholesterol homeostasis, its involvement in the development of AP remains unreported. We conducted this study to identify the pivotal role of Soat2 in AP using transcriptomic databases. Subsequently, we confirmed its alterations through both in vitro and in vivo experimental models. Furthermore, we performed intervention with the Soat2 inhibitor avasimibe to evaluate pancreatic tissue pathology and serum enzymatic levels and observe inflammatory cell infiltration through immunohistochemistry. Additionally, changes in indicators related to ferroptosis were also observed. The results showed that in the AP mouse model, the protein and mRNA levels of Soat2 were significantly increased. Following avasimibe administration, there was a decrease in serum amylase levels, reduction in pancreatic tissue pathological damage, and attenuation of inflammatory cell infiltration. Furthermore, avasimibe administration resulted in downregulation of ferroptosis-related indicators. In conclusion, our findings suggest that the Soat2 inhibitor avasimibe protects against AP in mice through inhibition of the ferroptosis.

2024-03-01·Comparative Biochemistry and Physiology Part D: Genomics and Proteomics

Insights into sequence characteristics and evolutionary history of DGATs in arthropods

Article

作者: Wu, Xugan ; Wang, Zongji ; Shu-Chien, Alexander Chong ; Wei, Maolei ; Huang, Baoyou ; Ge, Chutian ; Yi, Peng ; Naz, Saira

Triacylglycerol (TAG) is crucial in animal energy storage and membrane biogenesis. The conversion of diacylglycerol (DAG) to triacylglycerol (TAG) is catalyzed by diacylglycerol acyltransferase enzymes (DGATs), which are encoded by genes belonging to two distinct gene families. Although arthropods are known to possess DGATs activities and utilize the glycerol-3-phosphate pathway and MAG pathway for TAG biosynthesis, the sequence characterization and evolutionary history of DGATs in arthropods remains unclear. This study aimed to comparatively evaluate genomic analyses of DGATs in 13 arthropod species and 14 outgroup species. We found that arthropods lack SOAT2 genes within the DGAT1 family, while DGAT2, MOGAT3, AWAT1, and AWAT2 were absent from in DGAT2 family. Gene structure and phylogenetic analyses revealed that DGAT1 and DGAT2 genes come from different gene families. The expression patterns of these genes were further analyzed in crustaceans, demonstrating the importance of DGAT1 in TAG biosynthesis. Additionally, we identified the DGAT1 gene in Swimming crab (P. trituberculatus) undergoes a mutually exclusive alternative splicing event in the molt stages. Our newly determined DGAT inventory data provide a more complete scenario and insights into the evolutionary dynamics and functional diversification of DGATs in arthropods.

项与 SOAT2 相关的新闻（医药）

2024-02-06

·生物谷

《自然》重磅 | 广州出生队列揭示宫内环境和遗传差异对子代健康影响

妊娠是一个奇妙的过程，胎儿生长发育受到母体宫内环境和胎儿自身遗传影响，但是，宫内环境和遗传效应对胎儿的生长发育到底起怎样的作用尚不清楚。2024年1月，广州出生队列在国际顶尖期刊《自然》（Nature）上发表题为“The Born in Guangzhou Cohort Study Enables Generational Genetic Discoveries”的论著，揭示了遗传因素和宫内环境对子代健康的影响。DOI：10.1038/s41586-023-06988-4广州出生队列利用 4,053 名研究对象，采用跨代孟德尔随机化方法，创新性地建立传递和未传递等位基因的单体型遗传得分，清晰地剥离宫内环境和遗传对胎儿生长发育的效应，明确了妊娠期暴露对胎儿生长的潜在因果关系。例如，在扣除了代际遗传的影响后，母亲孕期空腹血糖和子代出生体重仍存在因果关联（母亲空腹血糖每增加1mmol/L，子代出生体重增加516.2g）。此外，我们还首次发现了母亲孕期总胆汁酸与子代出生身长之间存在因果关系，母亲孕期总胆汁酸每升高1mmol/L，子代出生身长减少0.42cm。图1. 跨代孟德尔随机化分析示意图（左）；影响出生体重的母体宫内环境和子代遗传效应（右）利用GWAS研究，我们新发现了东亚人群所特有的调控基因，如与孕妇孕期总胆汁酸相关的SLC10A1基因(rs2296651)，与子代脐血低密度脂蛋白(LDL)相关的SOAT2基因(rs137994041)。孕妇携带rs2296651-A基因型时，妊娠期间发生胆汁淤积症的风险增加3.55倍。进一步分析发现影响母儿脂质代谢的遗传信号存在差异，如CELSR2基因会影响孕妇外周血LDL水平，而SOAT2基因则会影响子代脐血中的LDL水平，该结果揭示了人体调控脂类代谢的基因可能在特定的年龄发挥遗传效应。这一发现为在不同年龄阶段更准确地评估个体脂代谢相关疾病风险提供全新的遗传学基础。图2. 脂代谢的年龄特异性遗传效应同时，我们系统分析了研究人群习惯使用的方言与遗传信息的关系。结合古人遗传信息进行分析，发现广州出生队列人群中的粤语人群有着明显的北方古人痕迹，即从遗传上看，现代粤语人群总体上是北方中国人和现代南方中国人的混合体。这为我们更深入了解现代南方人群的遗传多样性和演变提供了宝贵的线索，也为理解华南地区方言和人口演变的相互关系提供了有力支持。图3. 广州出生队列揭示南方人群的群体结构及历史广州出生队列（The Born in Guangzhou Cohort Study, BIGCS）是基于广州市妇女儿童医疗中心的一项大型中国普通人群亲子前瞻性队列，是目前全国入组人数最多，随访管理完善的出生队列。截至2023年底已入组家庭数超过5.8万个，生物样本库累计入库超过290万人份，实现全流程信息化管理。2018年Nature杂志以《中国新星带来的巨型数据流星雨》为题，报道了广州出生队列。【Nature 新闻】中国儿童健康研究领域的“新生巨星”带来的数据流星雨广州出生队列研究团队此次发表在国际顶级科学期刊Nature上的跨代孟德尔随机化方法，为更好地认识母儿健康的代际传递研究提供了新的范式和方法学支撑，也为研究宫内暴露、遗传和早期生活经历之间相互作用，及其塑造长期健康的机制奠定了关键技术基础。随着研究进一步拓展，我们将更深入和全面地分析生命早期一系列环境和遗传因素的复杂相互作用，以及它们影响出生结局、儿童期和成年期健康的时间窗及作用机制。*该项目已通过伦理审查，符合国家法律法规及伦理规范，并严格保护参与者隐私及数据安全，并通过中国科技部人类遗传资源管理办公室的批准。来源 | 广州出生队列本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床研究