更新于：2024-09-19

PLB1

更新于：2024-09-19

基本信息

别名

FLJ30866、hPLB、Lysophospholipase

+ [9]

简介

Calcium-independent membrane-associated phospholipase that catalyzes complete diacylation of phospholipids by hydrolyzing both sn-1 and sn-2 fatty acyl chains attached to the glycerol backbone (phospholipase B activity) (By similarity). Has dual phospholipase and lysophospholipase activities toward diacylphospholipids. Preferentially cleaves sn-2 ester bonds over sn-1 bonds. Acts as a lipase toward glycerolipid substrates (By similarity). Hydrolyzes fatty acyl chains of diacylglycerols with preference for the sn-2 position and of triacylglycerols with not positional selectivity (By similarity). May also hydrolyze long chain retinyl esters such as retinyl palmitate (By similarity). May contribute to digestion of dietary phospholipids, glycerolipids and retinoids, facilitating lipid absorption at the brush border (By similarity).

关联

100 项与 PLB1 相关的临床结果

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100 项与 PLB1 相关的转化医学

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0 项与 PLB1 相关的专利（医药）

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402

项与 PLB1 相关的文献（医药）

2024-12-01·Molecular Genetics and Genomics

Identification of plb1 mutation that extends longevity via activating Sty1 MAPK in Schizosaccharomyces pombe

Article

作者: Ihara, Kunio ; Aiba, Hirofumi ; Maekawa, Yasukichi ; Tani, Motohiro ; Matsui, Kotaro ; Okamoto, Keisuke ; Ohtsuka, Hokuto ; Shimasaki, Takafumi

To understand the lifespan of higher organisms, including humans, it is important to understand lifespan at the cellular level as a prerequisite. So, fission yeast is a good model organism for the study of lifespan. To identify the novel factors involved in longevity, we are conducting a large-scale screening of long-lived mutant strains that extend chronological lifespan (cell survival in the stationary phase) using fission yeast. One of the newly acquired long-lived mutant strains (No.98 mutant) was selected for analysis and found that the long-lived phenotype was due to a missense mutation (92Phe → Ile) in the plb1⁺ gene. plb1⁺ gene in fission yeast is a nonessential gene encoding a homolog of phospholipase B, but its functions under normal growth conditions, as well as phospholipase B activity, remain unresolved. Our analysis of the No.98 mutant revealed that the plb1 mutation reduces the integrity of the cellular membrane and cell wall and activates Sty1 via phosphorylation.

2024-06-03·Journal of Applied Microbiology

A novel diterpenic derivative produced by Streptomyces chrestomyceticus ADP4 is a potent inhibitor of biofilm and virulence factors in Candida albicans and C. auris

Article

作者: Ali, Mohd ; Dubey, Ashok K ; Singh, Radha ; Shukla, Jyoti

AbstractAimIsolation, identification, structural and functional characterization of potent anti-Candida compound with specific antagonistic activities against significant human pathogens, Candida albicans and C. auris.Methods and ResultsThe compound (55B3) was purified from the metabolites produced by Streptomyces chrestomyceticus ADP4 by employing column chromatography. The structure of 55B3 was determined from the analyses of spectral data that included LCMS, nuclear magnetic resonance, FTIR, and UV spectroscopies. It was identified as a novel derivative of diterpenic aromatic acid, 3-(dictyotin-11′-oate-15′α, 19′β-olide)-4-(dictyotin-11′-oate-15″α, 19″β-olide)-protocatechoic acid. The compound displayed potent antifungal and anti-biofilm activities against C. albicans ATCC 10231 (Minimum Inhibitory Concentration, MIC90:14.94 ± 0.17 μgmL−1 and MBIC90: 16.03 ± 1.1 μgmL−1) and against C. auris CBS 12372 (MIC90: 21.75 ± 1.5 μgmL−1 and Minimum Biofilm Inhibitory Concentration, MBIC90: 18.38 ± 1.78 μgmL−1). Further, pronounced inhibition of important virulence attributes of Candida spp., e.g. yeast-to-hyphae transition, secretory aspartyl proteinase and phospholipase B by 55B3 was noted at subinhibitory concentrations. A plausible mechanism of anti-Candida action of the compound appeared to be the inhibition of ergosterol biosynthesis, which was inhibited by 64 ± 3% at the MIC90 value. The non-cytotoxic attribute of the compound was noted in the liver cell line (HepG2 cells).ConclusionThe present work led to the discovery of a novel diterpenic derivative produced by S. chrestomyceticus ADP4. The compound displayed potent anti-Candida activity, particularly against the two most significant human pathogens, C. albicans and C. auris, which underlined its significance as a potential drug candidate for infections involving these pathogens.

2024-05-20·Investigative Ophthalmology & Visual Science

Association of Novel Loci With Keratoconus Susceptibility in a Chinese Genome-Wide Association Study

Article

作者: Zang, Yonghao ; Gu, Yuwei ; Ren, Shengwei ; Fan, Qi ; Zheng, Xiaodong ; Pang, Chenjiu ; Xu, Liyan ; Yang, Kaili ; Sun, Liangdan ; Yin, Shanshan ; Yuan, Yi ; Yin, Chenchen

PurposeKeratoconus (KC) is a progressive corneal disease that can lead to corneal blindness if not properly managed. The purpose of this study was to identify genetic associations with KC in China and to investigate whether these genetic variants are associated with corneal thickness and corneal curvature in KC cases.MethodsA genome-wide association study was conducted on 853 patients with KC and 6248 controls. The KC cases were genotyped with the Illumina Infinium Human Asian Screening Array BeadChip, and the controls were genotyped with the Illumina Infinium Human Global Screening Array BeadChip. Genetic associations with KC, as well as correlations between the positive variants and corneal parameters including central corneal thickness (CCT) and mean keratometry (Km), were compared using PLINK version 1.90.ResultsOur present study identified four single-nucleotide polymorphisms (SNPs) within four risk loci (PTGER3: rs2300163, EYA1: rs1077435, ASS1: rs141365191, and CHTF8: rs3743680) associated with KC in Chinese patients that reached genome-wide significance. Among the identified SNPs with P < 1.00 × 10-4, seven SNPs (FOSL2-PLB1: rs12622211, RXRA-COL5A1: rs3118515, rs3132306, rs1536482, rs3118520, KAT6B: rs192187772, RAP2A-IPO5: rs41361245) were observed to be associated with CCT, and one SNP (USP13: rs6767552) was found to be associated with Km.ConclusionsIn the first genome-wide association study of KC with a relatively large study population in China, we identified four SNPs in four risk loci associated with the disease. The findings enriched the understanding of genetic susceptibility to KC and provided new insights into the genetic etiology of the disease.

项与 PLB1 相关的新闻（医药）

2024-03-13

·CPHI制药在线

天然产物抗念珠菌作用机制研究进展（上）

关注并星标CPHI制药在线念珠菌感染是临床最常见的机会性真菌感染之一，好发于老年人群、癌症化疗、移植术后、HIV感染等免疫低下人群。由于唑类、多烯类、棘白菌素类等传统抗真菌剂的广泛使用，天然耐药性念珠菌株的出现以及非白念珠菌感染比例增加，临床念珠菌耐药现象日渐严重。天然产物以其独特的化学多样性和生物活性而闻名，几个世纪以来一直被广泛用于治疗各种疾病。据统计，临床的一线抗真菌药物通常是天然产品或其衍生品。近年来，抗真菌天然产物的开发取得了重大进展，已发现相当数量的天然分子对不同种类的念珠菌具有治疗作用。如从植物组织中提取出的化学结构明确的生物活性分子及其衍生物对多种念珠菌具有显著抑制作用，且具有来源广泛、不良反应小、适合长期或预防性使用等多方面优势，成为新型抗真菌剂的重要来源。抗念珠菌天然产物中，真菌代谢物是主要来源，其次是植物。这些化合物大多属于生物碱、聚酮类、萜类、酚类、大环内酯类和多肽类。其中，萜类化合物含量最高，其次是生物碱和聚酮类化合物。①萜类化合物主要是高等植物和内生真菌的代谢产物，具有抗念珠菌活性的萜类化合物包括单萜、倍半萜、二萜和三萜。研究表明，从有柄灵芝中分离的14种三萜类化合物增加了耐氟康唑白念珠菌对氟康唑的敏感性，其中部分能明显抑制白念珠菌。从樟子松挥发油中分离出的倍半萜对白念珠菌、光滑念珠菌及克柔念珠菌均有抑菌作用。②生物碱是存在于生物体内的含氮碱性化合物，具有显著的生物活性。抗念珠菌的生物碱种类繁多，主要包括吲哚类、吡啶类、喹诺酮类等。吲哚类及喹诺酮类具有相对广泛的抗真菌谱，但它们的抑菌活性通常是中等。相比之下，已报道的吡啶生物碱显示出很强的抗真菌活性。③聚酮类抗念珠菌的聚酮类化合物大部分是从真菌代谢产物中分离得到的。如从红树植物内生真菌茎点霉属中分离得到部分聚酮化合物对白念珠菌显示较强的抗菌活性，MIC50值为2.62μg/mL。天然产物抗念珠菌的作用机制天然产物抗念珠菌的作用机制主要包括抑制念珠菌毒力因子，如抑制念珠菌黏附与侵袭、酵母态-菌丝态形态转换、生物膜形成、水解酶合成与分泌等；影响念珠菌细胞壁、细胞膜和线粒体等细胞结构变化；诱导念珠菌细胞凋亡；抑制念珠菌药物靶酶与外排泵表达；此外也有部分天然产物通过调节免疫增强抗念珠菌作用。 01抑制黏附与侵袭作用白念珠菌的黏附是其发挥侵袭作用及形成生物膜的关键性第一步，植物活性成分抗念珠菌黏附作用可主要通过细胞实验进行证实。即通过将念珠菌与口腔黏膜上皮细胞共培养，观察在植物活性成分作用下，念珠菌在口腔黏膜上皮细胞表面的黏附情况。研究发现，400μg/mL 丹皮酚和1μg/mL氟康唑单独应用时，白念珠菌对人口腔黏膜上皮细胞的黏附率分别为(93.33±4.84)%与(91.67±3.45)%，而联合应用时其黏附率仅为(38.33±1.51)%，表明丹皮酚可与氟康唑协同抑制白念珠菌对人口腔黏膜上皮细胞的黏附。此外，研究表明，肉桂醛、小檗碱单独使用以及与氟康唑联用时，既可抑制白念珠菌芽管形成，还可显著抑制其对人口腔黏膜上皮细胞的黏附。其机制为肉桂醛、小檗碱与氟康唑协同干扰了白念珠菌芽管胞壁蛋白的合成及其相关基因的调控，从而抑制了白念珠菌芽管的形成，并降低了其对宿主细胞的黏附能力。另有学者通过选取人克隆结直肠腺癌细胞系(Caco-2)与白念珠菌共培养，并采用细胞膜探针(DiI) 染色法，评估了网脊衣酸 B对白念珠菌侵袭宿主细胞能力的影响。结果表明，网脊衣酸B与氟康唑单独应用时，细胞内菌丝侵袭率分别为(68±34)%及(57±16)%，而当两种药物联用后，细胞内菌丝侵袭率可显著减少至(25±16)%，证实植物活性成分网脊衣酸B具有抗念珠菌侵袭作用。 02抑制酵母态-菌丝态形态转换酵母态-菌丝态形态转换是白念珠菌发挥致病性的基础。白念珠菌可通过由酵母态转化为菌丝态，对宿主细胞产生黏附、穿刺和侵袭作用，进而发挥其致病性。涉及到的相关信号通路主要包括：cAMP/PKA信号通路、MAPK信号通路、Rim101介导的pH信号通路、及Tup1介导的负调通路等。研究显示，当血根碱浓度为0.8μg/m时，Spider培养基中的白念珠菌全部保持酵母态，未见菌丝生成；而当血根碱浓度达1.6μg/mL时，白念珠菌cAMP信号通路相关基因ALS3、HWP1、ECE1、HGC1、CYR1 的表达水平均显著下调。研究发现，4μg/mL 的厚朴酚与和厚朴酚可显著抑制白念珠菌菌丝形成，当其浓度达到16μg/mL时，Spider培养基中的白念珠菌未见菌丝生成，其可能机制为厚朴酚与和厚朴酚抑制了Ras1-cAMP-Efg1信号通路相关基因RAS1、EFG1、TEC1 和CDC35 的表达。群体感应分子法尼醇可通过抑制腺苷酸环化酶活性，作用于Ras1-Cyr1-cAMPEfg1信号通路，进而抑制念珠菌酵母态-菌丝态形态转换及生物膜形成；而酪醇则可以促进其菌丝及生物膜形成。另有研究发现，穿心莲内酯可影响白念珠菌群体感应分子法尼醇与酪醇的分泌量，并且对法尼醇呈负调作用，对酪醇呈正调作用，且该成分可使群体感应分子编码基因CHK1和PBS2明显下调，最终对白念珠菌酵母态-菌丝态形态转换及生物膜形成产生显著抑制作用。 03天然产物对念珠菌生物膜的影响念珠菌生物膜的形成过程可大致分为4个阶段：宿主表面黏附；念珠菌细胞的增殖；菌丝形成及细胞外基质的产生；生物膜成熟后菌体的扩散及其他部位的定植。研究显示，植物活性成分的抗念珠菌作用机制包括抑制念珠菌生物膜形成过程、破坏念珠菌生物膜空间结构、影响念珠菌生物膜细胞扩散等。研究发现，小檗碱对白念珠菌、克柔念珠菌、都柏林念珠菌、光滑念珠菌生物膜的初始形成期至成熟期(6h、12h、24h、48h)均有抑制作用，其中对48h生物膜抑制作用最强。激光共聚焦显微镜及3D 重建后观察发现，小檗碱可显著破坏生物膜的空间结构，使细胞排列松散，密度降低，生物膜厚度变薄。黄芩素是黄芩的主要活性成分，研究表明它可通过减少CSH1的表达而降低生物膜的表面疏水性，从而减少黏附，抑制白念珠菌生物膜的形成。从苔藓类植物中提取的具有大环双联苄结构的化合物Riccardin D可通过下调菌丝特异基因ALS1、ALS3、ECE1、EFG1、HWP1和CDC35的表达并抑制了Ras-cAMP-EFG途径，从而延缓了菌丝的形成，导致生物膜成熟缺陷。莲碱是从天仙藤茎中分离得到的一种异喹啉类生物碱，通过相似途径发挥抗念珠菌生物膜作用。酸模属植物根部提取的nepodin通过抑制菌丝和生物膜相关基因(ECE1、HGT10、HWP1和UME6)的表达以及增加运输基因(CDR4、CDR11和TPO2)的表达可抑制白念珠菌、光滑念珠菌、近平滑念珠菌等念珠菌生物膜的形成。大叶藤黄中分离得到的二苯甲酮类化合物xanthochymol和garcinol，能有效地抑制芽管萌发，诱导早期和成熟的生物膜细胞凋亡，从而直接杀死菌丝和生物膜。 04抑制水解酶合成与分泌白念珠菌毒力相关水解酶主要包括分泌性天冬氨酸蛋白酶(secretedaspartylproteinase，Sap)、磷脂酶 (phospholipase，PL) 和脂肪酶 (lipase，Lip)等。水解酶可介导白念珠菌黏附、侵袭宿主细胞，同时还可裂解宿主免疫应答相关分子，协助白念珠菌逃避宿主的免疫防御机制。多种植物活性成分可通过下调水解酶相关编码基因，抑制水解酶合成，进而减少其分泌。研究发现紫草素可呈浓度依赖性抑制白念珠菌磷脂酶分泌，8μg/m的紫草素可使PLB1和PLB2 基因的相对表达量降低56.4%和 61.4%，且16μg/mL 的紫草素可使白念珠菌磷脂酶分泌量下降56.3%。另有研究发现，当鱼腥草素钠浓度达240 mg/L时，可显著抑制磷脂酶编码基因PLB1和PLB2的表达。与此相反，一些植物活性成分还可通过上调水解酶相关基因表达而发挥作用。参考资料 [1]余宇,佘晓东,刘维达.抗念珠菌天然产物的研究进展[J].中国真菌学杂志,2023,18(02):183-187. [2]解雨飞,周培茹,华红等.植物活性成分抗念珠菌作用机制研究进展[J].中国真菌学杂志,2022,17(04):315-318+329. 作者简介：小米虫，药品质量研究工作者，长期致力于药品质量研究及药品分析方法验证工作，现就职于国内某大型药物研发公司，从事药品检验分析及分析方法验证。【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

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