Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Transcriptome analysis of the effect of pyrroloquinoline quinone disodium（PQQ·Na2） on reproductive performance in sows during gestation and lactation

Background: Pyrroloquinoline quinone(PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium(PQQ·Na2) on reproductive performance in sows.Results: Dietary supplementation with PQQ·Na2 significantly increased the total number of piglets born, the number of piglets born alive and the born alive litter weight. It also increased the antioxidant status in the placenta, plasma and milk. The concentration of NO was significantly increased in the plasma and placenta. RNA-seq analysis showed that462 unigenes were differentially expressed between the control(Con) treatment and PQQ treatment groups.Among these unigenes, 199 were upregulated, while 263 unigenes were downregulated. The assigned functions of the unigenes covered a broad range of GO categories. Reproduction(27, 7.03%) and the reproduction process(27, 7.03%) were assigned to the biological process category. By matching DEGs to the KEGG database, we identified 29 pathways.Conclusions: In conclusion, dietary supplementation with PQQ·Na2 in gestating and lactating sows had positive effects on their reproductive performance.

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Background:Oxidative stress is a main cause of piglet gut damage and diarrhea.Pyrroloquinoline quinone(PQQ),is a novel redox cofactor with antioxidant properties.However,the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood.Therefore,the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line(IPEC-J2)challenged with H_(2)O_(2).Results:Experiment 1,144 Duroc×Landrace×Yorkshire pigs(weaned at 28 d)were allocated to four groups:received a basal diet(control)and diets supplemented with 0.15%,0.30%and 0.45%PQQ,respectively.On d 28,growth performance,diarrhea incidence and redox factors were measured.Experiment 2,IPEC-J2 were treated with or without PQQ in the presence or absence of H_(2)O_(2)for indicated time points.Experiment 3,IPEC-J2 were transfected with or without Nrf2 siRNA,then treated according to Experiment 2.The cell viability,redox factors,protein of tight junctions and Nrf2 pathway were determined.In vivo,PQQ supplementation demonstrated dose-related improvements in average daily gain,and gain to feed ratio(Linear P<0.05).During d 0–28,compared to controls,0.45%PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum,and increased concentration of SOD in liver;0.3%PQQ supplementation decreased ileal and liver MDA concentration;and 0.15%PQQ supplementation decreased ileal MDA concentration(P<0.05).In vitro,compared to cells cultured with H_(2)O_(2),pre-treatment with PQQ increased cell viability,tight junction proteins expression including ZO-1,ZO-2,Occludin and Claudin-1;and decreased ROS concentration and level of Caspase-3(P<0.05);as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2,HO-1.Notably,Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H_(2)O_(2)-induced intracellular changes.Conclusions:PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.

Protective Effect of Pyrroloquinoline Quinone on TNF-α-induced Mitochondrial Injury in Chondrocytes

Osteoarthritis(OA)is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity.As a bacterial synthesis of quinine,pyrroloquinoline quinone(PQQ)is a strong redox cofactor with a variety of biological benefits,including antioxidant,anti-inflammation-induced mitochondrial metabolism regulation.This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes.Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α50 ng/mL,TNF-α50 ng/mL+PQQ 10µmol/L for 24 h.Then,morphological study,functional study and mechanism study were taken.The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ,evidenced by elevated number of mitochondria,well-kept mtDNA integrity,preserved ATP level,reestablished mitochondrial membrane potential,and prevented mitochondrial function.The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-αand the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α.PQQ might be a potential chemical for OA intervention.

Effect of dietary supplementation of pyrroloquinoline quinone disodium on growth performance, meat quality and antioxidative ability of broilers

This study was conducted to investigate the effect of dietary supplementation with pyrroloquinoline quinone(PQQ) in the form of PQQ disodium(PQQ·Na2) on the growth performance, carcass traits, meat quality and antioxidative ability of broilers. A total of 720 one-d-old Arbor Acres male broilers were randomly allocated to 1 of 6 treatments with 8 replicates of 15 birds per replicate in a completely randomized design. Birds were fed a PQQ·Na2-unsupplemented corn-soybean meal basal diet(control) or the basal diet supplemented with 0.1, 0.2, 0.3, 0.4 or 0.5 mg PQQ·Na2 kg-1 for 42 d. Compared with the control chicks, the chicks fed the diets supplemented with PQQ·Na2 had lower(P<0.05) feed:gain(F/G) during the grower phase and drip losses of breast muscles on day 42. As supplemental PQQ·Na2 level increased, plasma total antioxidant capacity(T-AOC) on d 42, liver T-AOC on d 21 and heart T-AOC on d 21 and 42 increased linearly(P<0.05), but malondialdehyde concentrations in plasma, liver and heart on d 21 or 42 decreased linearly(P<0.001) or quadratically(P<0.005). The results from the present study indicate that dietary supplemental PQQ·Na2 can improve antioxidant ability and meat quality of broilers, and in general, it is implied that the optimal supplemental PQQ·Na2 level is 0.1 mg kg-1 of diet for broilers from 1 to 42 d of age.

新食品原料呲咯喹啉醌二钠盐固体饮料免疫功能作用的研究

目的:研究呲咯喹啉醌二钠盐固体饮料的免疫功能作用。方法:呲咯喹啉醌二钠盐低、中、高剂量组分别经口灌胃0.125 g·kg^(-1)、0.250 g·kg^(-1)、0.500 g·kg^(-1)受试物,对照组、模型组灌胃等量体积的生理盐水,连续30 d,考察各组小鼠免疫器官指数、碳廓清能力、巨噬细胞吞噬能力以及脾NK细胞活性。结果:与模型小鼠相比,经呲咯喹啉醌二钠盐灌胃30 d后,呲咯喹啉醌二钠盐各剂量组免疫器官指数上升,碳廓清能力、巨噬细胞吞噬能力均提升,脾NK细胞活性增强,其中呲咯喹啉醌二钠盐中、高剂量组变化明显(P<0.05,P<0.01),与模型组有显著差异。结论:呲咯喹啉醌二钠盐可通过调节非特异性免疫指标,达到调节免疫功能的作用。

PQQ和IAA促生因子对Rahnella aquatilis HX2菌株促生机理研究

【目的】Rahnella aquatilis HX2菌株能合成吡咯喹啉醌(PQQ)和吲哚乙酸(IAA),探明PQQ与IAA在HX2菌株促生作用中的作用与机理。【方法】通过试管苗试验、温室砂培试验,分别以纯品PQQ、纯品IAA、HX2菌株及PQQ合成缺失突变体及互补菌株等处理接种玉米,对各处理的玉米生长量、营养以及根形态方面的影响进行检测和分析。【结果】与空白对照相比,PQQ、IAA纯品处理均能在促进玉米生长方面均有好的效果,HX2处理在玉米生物量(株高、鲜重和干重)、玉米营养(全N、全P、全K)摄入有显著提高,处理效果更好;PQQ合成缺失突变体MH15处理,虽对玉米鲜重、干重、全N、全P与对照相比有促进作用,但与HX2和互补菌株CMH15(pqq)处理玉米的促生效果相比较低。纯品PQQ、IAA处理主要提高了其细根长、中根长、总根长的长度和根表面积增加,但其根平均直径降低;而HX2菌株处理增加了其细根长、中根长、粗根长的长度,使玉米根系不仅伸长,且根系变粗。【结论】PQQ可作为直接促生因子和IAA,共同参与了HX2菌株对增加玉米生物量,提高玉米营养的摄入,促进其根形态等方面起到关键调控作用,明确了HX2菌株-PQQ-玉米、HX2菌株-IAA-玉米之间的相互作用。

低温胁迫下PQQ对黄瓜幼苗子叶防御系统的影响

报道了低温胁迫下吡咯喹啉醌（ＰｙｒｒｏｌｏｑｕｉｎｏｌｉｎｅＱｕｉｎｏｎｅ，ＰＱＱ）对黄瓜幼苗子叶超氧化物岐化酶（ＳＯＤ），抗坏血酸过氧化物酶（ＡｓＡＰＯＤ）和谷胱甘肽（ＧＳＨ）含量的影响，并与常规的外源活性氧清除剂８－羟基喹啉（８－ＨＱ），抗坏血酸（ＡｓＡ）进行了比较．结果表明，ＰＱＱ能提高ＳＯＤ，ＡｓＡＰＯＤ活性，增加ＧＳＨ含量．缓解电解质泄漏，减缓质脂过氧化作用．ＰＱＱ可作为活性氧清除剂，调节生物体内自由基代谢平衡，提高植物的抗逆性．

PQQ对四氯化碳和乙醇引起大鼠肝损伤的保护作用

将大鼠分成 5组 ,采用灌胃方式 ,连续 14d分别灌入 PQQ-水溶液、PQQ -乙醇溶液、乙醇溶液和生理盐水溶液 (阴性和阳性对照两组 ) ,尔后 ,除阴性对照组外 ,均灌入 CCL4.检测结果表明 :PQQ可明显降低大鼠血清中 GPT、GOT以及肝组织中 MDA的含量 ,可减轻肝细胞水变性、脂肪变性和肝细胞坏死的程度 ,由此说明 :PQQ对 CCl4和乙醇引起的肝损伤有一定的保护作用 .

两种甲醇脱氢酶在食甲基杆菌甲醇代谢中的作用

本研究以食葡糖食甲基杆菌MP688(Methylobacterium glucophilum MP688)的吡咯喹啉醌(pyrroloquino-line quinone,PQQ)高产突变株J1-1为研究对象,通过生物信息学分析从基因组上找到两个甲醇脱氢酶(methanol dehydrogenase,MDH)基因mpq0771和mpq2496。考察了Ca^(2+)及La^(3+)对菌体生长、PQQ合成、MDH表达及酶活力的影响,并研究两种酶在甲醇代谢中的作用。结果显示:Ca^(2+)和La^(3+)均能促进J1-1菌体生长,且在菌体快速生长的情况下导致PQQ合成下降;Ca^(2+)存在时,菌株J1-1中mpq0771表达量较高,添加La^(3+)后mpq0771表达受到阻遏,但增强了mpq2496表达,菌体MDH总活力也有所提高;敲除菌J1-1Δmpq0771不能利用甲醇生长,添加La^(3+)后可利用甲醇生长并能合成PQQ,且能检测到MDH活性。mpq0771编码产物是Ca^(2+)依赖的MDH,mpq2496编码产物是严格依赖La^(3+)的MDH,且La^(3+)能够诱导mpq2496表达并替代mpq0771发挥甲醇脱氢酶的作用。

磁性纳米分子印迹聚合物的制备及其对生物体内PQQ-DA痕量产物的研究

以磁性Fe_3O_4为内核,对磁性纳米粒子表面进行包裹和修饰,制备了对吡咯并喹啉醌-多巴胺(PQQ-DA)具有高识别性、高选择性的磁性纳米分子印迹材料,并结合超高效液相色谱-质谱(UPLC-MS)测定了生物体内PQQ-DA的含量。结果显示,PQQ-DA在0.02～0.1 mg/mL范围内呈良好的线性关系,相关系数(r^2)为0.996 6,检出限为0.2×10^(-11) mg/mL,加标回收率为88.7%～95.5%,相对标准偏差为2.6%～3.2%。该方法灵敏度高、重复性好,可用于生物体内PQQ-DA痕量产物的检测。

依赖新辅基PQQ甲醇脱氢酶的研究

生长在以甲醇作唯一碳源的甲基营养菌（Ｍｅｔｈｙｌｏｔｒｏｐｈｉｃｂａｃｔｅｒｉａ）Ｎｏ．２细胞，经超声波破碎，缓冲液抽提，ＤＥＡＥ－和ＣＭ－纤维素柱层析等纯化步骤，可得到纯化的甲醇脱氢酶（ＭＤＨ），其比活力为５．７ｕ／ｍｇ．该酶进行不连续聚丙烯酰胺凝胶电泳后，用相应的试剂分别染色，其蛋白质，酶活性和醌蛋白谱带均呈现一条迁移距离相同的主带．该酶由两个β亚基（６０ｋｂ）和两个α亚基（１０ｋｂ）构成，每个α亚基束缚一个新辅基ＰＱＱ（吡咯喹啉醌）．光谱分析显示，２９０ｎｍ有一肩峰，３４５ｎｍ有一特征峰，４００ｎｍ有一平台．这些数据表明。

HPLC法测定吡咯喹啉醌(PQQ)中咪唑并吡咯喹啉(IPQ)的含量

目的:建立吡咯喹啉醌(PQQ)中IPQ的含量测定方法。方法:采用TCI Kaseisorb LC ODS 2000色谱柱(4.6mm×150mm,5μm);流动相为乙腈-缓冲溶液(配制10mmol的磷酸氢二钾和15mmol的四丁基溴化铵水溶液,用磷酸调节pH至7.4)[28∶72];紫外检测器,检测波长为259nm;流速为1.0mL/min;进样量为20μL。结果:IPQ在0.05μg/mL^0.2μg/mL范围内线性关系良好,相关系数大于0.999。IPQ的回收率在104%~113%之间,RSD最大为3%。结论:该方法具有良好的专属性、检测灵敏度、精密度、线性和准确度,适用于PQQ中IPQ的质量控制。

依赖PQQ的甲醇脱氢酶与甘氨酸作用后的进程曲线

从革蓝氏阴性甲基营养菌Ｎｏ．２细胞提取的甲醇脱氢酶（ＭＤＨ）是一种氧化还原酶，已证明其辅基是新辅基ＰＱＱ（吡咯喹啉醌），笔者在研究ＭＤＨ及其辅基的理化性质过程中，发现甘氨酸（ｇｌｙ）对ＭＤＨ影响极为特殊，随后，以此为出发点得到的试验数据，对解释目前国...

吡咯喹啉醌（PQQ）的研究进展

吡咯喹啉醌是一种与烟酰胺核苷酸、黄素核苷酸不同的新型辅基。近年来，荷兰、日本等学者对它进行了初步研究，而国内研究起步较晚，文章综述了吡咯喹啉醌的发现、分离纯化、鉴定、理化性质以及生理功能，这有利于进一步研究吡咯喹啉醌的分布、产生机理、生物学性质、生理功能及其应用。这将对促进酶学学科的发展具有重要的理论和实践意义。

新辅基吡咯喹啉醌(PQQ)生物合成基因研究进展

吡咯喹啉醌（Ｐｙｒｏｌｏｑｕｉｎｏｌｉｎｅ－Ｑｕｉｎｏｎｅ，ＰＱＱ）是氧化还原酶的新辅基。它在细菌体内是由一组排列成簇的相关基因即ｐｑｑ基因控制合成的。根据不同细菌来源ｐｑｑ基因的同源性和对应关系，可将ｐｑｑ基因归为７类：簇基因１～７。在Ａｃｉｎｅｔｏｂａｃｔｅｒｃａｌｃｏａｃｅｔｉｃｕｓ中存在其中四个，ＫｌｅｂｓｉｅｌａＰｎｅｕｍｏｎｉａｅ和ＭｅｔｈｙｌｏｂａｃｔｅｒｉｕｍＯｒｇａｎｏｐｈｉｌｕｍＤＳＭ７６０中６个，而Ｍｅｔｈｙｌｏｂａｃｔｅｒｉｕｍｅｘ－ｔｏｒｑｕｅｎｓＡＭ１中存在全部７个簇基因。簇基因１编码一个由２２～２９年氨基酸组成的小肽，此小肽可能是ＰＱＱ的前体，簇基因２可能涉及ＰＱＱ跨膜转运，簇基因３可能负责ＰＱＱ合成的最后一步酶催化，簇基因５可能涉及ＰＱＱ合成中某种酶的辅因子合成，簇基因６和７可能负责小肽的加工。簇基因４功能还不清楚，但在Ｍ．ｅｘｔｏｒｑｕｅｎｓＡＭ１中簇基因３和４是以融合基因存在的。

Effects of PQQ on Protective System in Cucumber Cotyledons under Low Temperature Stress

The authors have studied the effects of Pyrroioguinloine quinone (PQQ) on superoxide dismutase (SOD), Ascorbid acid(AsA) peroxidase (AsAPOD), glutathion (GSH) and electrolytic leakage of cotyledon in cucumber seedling under low temperature stress, meanwhile, 8-hydroquinone (8-HQ) and AsA (activeoxiygen scavengers) have been made use of in comparison with PQQ. The results indicate that the activities of SOD, AsAPOD and content of GSH can be increased by PQQ. The relative conductivity of cotyledon in cucumber seedling is decreased for PQQ possesses the ability of cleaning up free redical of oxygen. We came to the conclusion that PQQ can act as a kind of active oxygen scavenger and adjust the metabolism on free radical of oxygen to balance in plants and enhance resistance finally in plants.

不同碳氮源配比对脱氮生丝微菌FJNU-R8生长和PQQ合成的影响

为了提高脱氮生丝微菌FJNU-R8生产PQQ的能力,以FJNU-R8为出发菌株,探究了不同碳氮源配比对其生长和PQQ合成的影响。通过探讨4种单一碳源和4种单一氮源对菌株生长和PQQ合成影响的基础上,进一步研究不同配比和不同浓度的复合碳源(甲醇∶甘油)/复合氮源(蛋白胨∶硫酸铵)对菌株生长和PQQ产量的影响。结果表明:以甲醇为单一碳源,OD_(650)仅为4.4,但PQQ产量43 mg·L^(-1),以甘油为单一碳源,OD_(650)可达9.8,但无PQQ产量;以硫酸铵为单一氮源,OD_(650)仅为4.2,但PQQ产量30 mg·L^(-1),以蛋白胨为单一氮源,OD_(650)可达7.7,但无PQQ产量。不同配比的复合碳源可以提高OD_(650),甘油比重越大,最终OD_(650)越高,但PQQ产量很低;不同配比的复合氮源可以提高生长速度,蛋白胨∶硫酸铵为40∶60时PQQ产量65 mg·L^(-1)。复合碳源(甲醇∶甘油为20∶80)的浓度越高,最终OD_(650)越高,但PQQ产量越低;复合氮源(蛋白胨∶硫酸铵为40∶60)浓度高于1 g·L^(-1)时,OD_(650)及PQQ产量无明显变化,最终OD_(650)约为7.5,PQQ产量约为45 mg·L^(-1)。结果显示复合碳源可提高OD_(650),复合氮源可提高PQQ产量,可为后续高产PQQ的碳氮源选择提供理论依据。

吡咯喹啉醌二钠对种公鸡抗氧化能力及睾丸组织形态的影响

本试验旨在研究饲粮添加不同水平的吡咯喹啉醌二钠(PQQ·Na2)对种公鸡抗氧化能力及睾丸组织形态的影响。试验选用96只健康的440日龄京红1号种公鸡,随机分为4组,每组6个重复,每个重复4只鸡,分别在基础饲粮中添加不同水平(0、0.5、1.0、2.0 mg/kg)的PQQ·Na2。试验期6周。结果显示:饲粮添加1.0和2.0 mg/kg PQQ·Na2可显著提高血清、肝脏、肾脏和睾丸中总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性(P<0.05),显著提高血清、肝脏、肾脏和睾丸清除羟自由基能力(P<0.05),显著提高血清、肝脏和睾丸清除超氧阴离子能力(P<0.05);显著降低血清、肝脏、肾脏和睾丸中丙二醛(MDA)含量(P<0.05);显著提高睾丸生精小管直径和生精上皮厚度(P<0.05)。由此可见,饲粮添加PQQ·Na2可改善种公鸡的抗氧化能力,提高种公鸡睾丸生精小管直径和生精上皮厚度,适宜添加水平为1.0 mg/kg。