Biochimie最新文献_第8页

Central nervous system pathways targeted by amylin in the regulation of food intake 淀粉样蛋白调节食物摄入量的中枢神经系统途径。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.012

Mohammed K. Hankir , Christelle Le Foll

{"title":"Central nervous system pathways targeted by amylin in the regulation of food intake","authors":"Mohammed K. Hankir , Christelle Le Foll","doi":"10.1016/j.biochi.2024.10.012","DOIUrl":"10.1016/j.biochi.2024.10.012","url":null,"abstract":"<div><div>Amylin is a peptide hormone co-released with insulin from pancreatic β-cells during a meal and primarily serves to promote satiation. While the caudal hindbrain was originally implicated as a major site of action in this regard, it is becoming increasingly clear that amylin recruits numerous central nervous system pathways to exert multifaceted effects on food intake. In this Review, we discuss the evidence derived from preclinical studies showing that amylin and the related peptide salmon calcitonin (sCT) directly or indirectly target genetically distinct neurons in the caudal hindbrain (nucleus tractus solitarius and area postrema), rostral hindbrain (lateral parabrachial nucleus), midbrain (lateral dorsal tegmentum and ventral tegmental area) and hypothalamus (arcuate nucleus and parasubthalamic nucleus) via activation of amylin and/or calcitonin receptors. Given that the stable amylin analogue cagrilintide is under clinical development for the treatment of obesity, it is important to determine whether this drug recruits overlapping or distinct central nervous system pathways to that of amylin and sCT with implications for minimising any aversive effects it potentially causes. Such insight will also be important to understand how amylin and sCT analogues synergize with other molecules as part of dual or triple agonist therapies for obesity, especially the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide, which has been shown to synergistically lower body weight with cagrilintide (CagriSema) in clinical trials.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 95-104"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress 人类抗凋亡蛋白 Bcl-2 和 Bcl-xL 保护酵母细胞免受老化诱导的氧化应激。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.009

Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek

{"title":"Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress","authors":"Ayşenur Güler , Berna Kavakcıoğlu Yardımcı , Nihal Şimşek Özek","doi":"10.1016/j.biochi.2024.10.009","DOIUrl":"10.1016/j.biochi.2024.10.009","url":null,"abstract":"<div><div>Aging is a degenerative, biological, and time-dependent process that affects all organisms. Yeast aging is a physiological phenomenon characterized by the progressive transformation of yeast cells, resulting in modifications to their viability and vitality. Aging in yeast cells is comparable to that in higher organisms in some respects; however, due to their straightforward and well-characterized genetic makeup, these cells present unique advantages when it comes to researching the aging process. Here, we assessed the impact of human anti-apoptotic Bcl-2 and Bcl-xL proteins on aging using a yeast model. The findings clearly showed that these proteins exhibited remarkable anti-aging properties in yeast cells. Our data indicate that the presence of both proteins enhanced the reproductive survival of aging cells, likely by effecting the components functioning as both pro- and anti-oxidants, depending on the stage of yeast cell lifespan. Both proteins partially protected yeast cells from aging-related morphological deformations and cellular damage during the aging period. In particular, Bcl-xL expressing yeast cells reached the maximum activity levels for almost all of the major antioxidant enzymes and the total antioxidant status on the 8th day of lifespan and could provide effective protection at the latest stage of the investigated aging period. The chemometric data analysis of IR spectra confirmed the findings of the morphological and biochemical analyses. In this regard, specifically, understanding the mechanism of action on the cellular redox state of Bcl-xL in yeast may facilitate comprehension of its indirect antioxidant function in higher eukaryotes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 69-83"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A set of microRNAs are differentially expressed in cachexic naked mole rat colony members after chronic heavy burden under normoxia 一组microrna在常氧条件下慢性重负荷裸鼹鼠群体成员中差异表达。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2025.01.010

MA Adrianov , M Bobrov , I Mamedov , V Manskikh , EV Sheval , AA Rachkova , AM Shelechova , CM Eldarov , OA Averina , MY Vyssokikh

{"title":"A set of microRNAs are differentially expressed in cachexic naked mole rat colony members after chronic heavy burden under normoxia","authors":"MA Adrianov , M Bobrov , I Mamedov , V Manskikh , EV Sheval , AA Rachkova , AM Shelechova , CM Eldarov , OA Averina , MY Vyssokikh","doi":"10.1016/j.biochi.2025.01.010","DOIUrl":"10.1016/j.biochi.2025.01.010","url":null,"abstract":"<div><div>Enrichment of the habitat of captive rodents <em>Heterocephalus glaber</em> (naked mole rats) to implement their innate behavioral pattern of digging dense soil in search of food, paradoxically led to the appearance of unusual animals in the colony. They showed signs of cachexia, distinguished from other animals by a lower temperature (from 31 °C to 26 °C) and body mass index with decreasing proportion of subcutaneous fat. This animal demonstrated aggressive feeding behavior, but didn't gain weight even after finishing experiment with intensive physical activity. In histochemical analysis of tissues from cachexic and normal animals of the same age and sex liver hyperlipofuscinosis was revealed and indicated that animals when being in a habitat with an increased oxygen content for them (21 % versus 8 % in their natural underground habitat), experienced severe oxidative stress during physical exercise. Stress led to a disruption of the body's regulatory systems, a sharp increase in metabolism even at rest, an overload of the cardiovascular and respiratory systems and damage to organs and tissues. To clarify the pathogenetic mechanism of the observed phenomenon, microRNA was extracted from the animal tissues and sequenced. Then bioinformatics analysis of differential expression of microRNAs between groups of healthy animals and animals with idiopathic cachexia was performed.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 83-90"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality 纳豆激酶的定点突变：揭示结构-功能关系以增强功能

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.09.014

Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur

{"title":"Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality","authors":"Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur","doi":"10.1016/j.biochi.2024.09.014","DOIUrl":"10.1016/j.biochi.2024.09.014","url":null,"abstract":"<div><div>Site-directed mutagenesis was employed to investigate the structure-function relationship of nattokinase (NK) and its effect on the enzymatic activity, thermostability, pH tolerance, and fibrinolytic properties of NK. Specific mutations (T270S, V271I, E262D, and A259T) were introduced within the nk gene, targeting regions predicted to be involved in substrate binding. The NK(E262D) mutant exhibited a significant increase in enzymatic activity (2-fold) and catalytic efficiency (2.2-fold) as assessed by N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide (Suc-AAPF-pNA) hydrolysis, compared to the wild type. <em>In silico</em> analysis supported these findings, demonstrating lower binding energy for the NK(E262D) mutant, suggesting stronger fibrin affinity. Thermostability assays revealed that NK(E262D) and NK(A259T) displayed exceptional stability, retaining enzyme activity at 60 °C. All mutants exhibited a broader pH tolerance range (pH 5.0–10.0) compared to the wild-type NK. The fibrinolytic activity assay revealed that the E262D mutant possessed the highest fibrinolytic activity (2414 U/mg), surpassing the wild-type. This study reported an NK variant with improved enzymatic activity, thermostability, and fibrinolytic properties.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 1-8"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP 生产人类肿瘤靶标极光激酶 b 与其结合伙伴 incenp 复合物的稳健方法。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.011

Jonna Mattsson , Per Rogne , Maréne Landström , Magnus Wolf-Watz

{"title":"Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP","authors":"Jonna Mattsson , Per Rogne , Maréne Landström , Magnus Wolf-Watz","doi":"10.1016/j.biochi.2024.10.011","DOIUrl":"10.1016/j.biochi.2024.10.011","url":null,"abstract":"<div><div>Protein kinases are key players in many eukaryotic signal transduction cascades and are as a result often linked to human disease. In humans, the mitotic protein kinase family of Aurora kinases consist of three members: Aurora A, B and C. All three members are involved in cell division with proposed implications in various human cancers. The human Aurora kinase B has in particular proven challenging to study with structural biology approaches, and this is mainly due to difficulties in producing the large quantities of active enzyme required for such studies. Here, we present a novel and <em>E. coli</em>-based production system that allows for production of milligram quantities of well-folded and active human Aurora B in complex with its binding partner INCENP. The complex is produced as a continuous polypeptide chain and the resulting fusion protein is cleaved with TEV protease to generate a stable and native heterodimer of the Aurora B:INCENP complex. The activity, stability and degree of phosphorylation of the protein complex was quantified by using a coupled ATPase assay, <sup>31</sup>P NMR spectroscopy and mass spectrometry. The developed production system enables isotope labeling and we here report the first <sup>1</sup>H–<sup>15</sup>N-HSQC of the human Aurora B:INCENP complex. Our developed production strategy paves the way for future structural and functional studies of Aurora B and can as such assist the development of novel anticancer drugs targeting this important mitotic protein kinase.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 129-140"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone 极性溶解物埃克托因和羟基埃克托因对热诱导蛋白质聚集的影响：以生长激素为例

IF 3.3 3区生物学

Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.006

Rūta Gruškienė, Jolanta Sereikaitė

{"title":"The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone","authors":"Rūta Gruškienė, Jolanta Sereikaitė","doi":"10.1016/j.biochi.2024.10.006","DOIUrl":"10.1016/j.biochi.2024.10.006","url":null,"abstract":"<div><div>The extremolytes ectoine and hydroxyectoine are osmolytes found in extremophilic microorganisms. They are stabilisers of proteins and other macromolecules, including DNA and lipids. The aim of the study was to investigate the effect of the additives on the heat-induced aggregation of mink growth hormone as a model protein. The first-order rate constants of protein aggregation were determined at 60 °C depending on the additive concentration and pH of the solution. The onset temperature of aggregation was also recorded using a circular dichroism spectropolarimeter. The study showed that the effect of the additives depended on the pH of the solution. The first-order rate constants of aggregation were lower when the protein molecule had a negative charge. The effect also depended on the structure of the extremolyte itself. When the protein molecule was positively charged, hydroxyectoine destabilised the mink growth hormone molecule and promoted the aggregation. The different effects of the additives were determined by the different interactions with the protein molecules, as shown by circular dichroism measurements and previously by fluorescence spectroscopy. Therefore, when using ectoine or hydroxyectoine for protein formulation, the effect of the additive should be carefully analysed for each protein individually.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 42-48"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The pentose phosphate pathway (PPP) in the glioma metabolism: A potent enhancer of malignancy 胶质瘤代谢中的戊糖磷酸途径（PPP）：恶性肿瘤的有力增强剂。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-31 DOI: 10.1016/j.biochi.2025.01.013

Cristina Trejo-Solís , Ángel Escamilla-Ramírez , Saúl Gómez-Manzo , Rosa Angélica Castillo-Rodriguez , Francisca Palomares-Alonso , Carlos Castillo-Pérez , Dolores Jiménez-Farfán , Aurora Sánchez-García , Juan Carlos Gallardo-Pérez

{"title":"The pentose phosphate pathway (PPP) in the glioma metabolism: A potent enhancer of malignancy","authors":"Cristina Trejo-Solís , Ángel Escamilla-Ramírez , Saúl Gómez-Manzo , Rosa Angélica Castillo-Rodriguez , Francisca Palomares-Alonso , Carlos Castillo-Pérez , Dolores Jiménez-Farfán , Aurora Sánchez-García , Juan Carlos Gallardo-Pérez","doi":"10.1016/j.biochi.2025.01.013","DOIUrl":"10.1016/j.biochi.2025.01.013","url":null,"abstract":"<div><div>The glioma hallmark includes reprogramming metabolism to support biosynthetic and bioenergetic demands, as well as to maintain their redox equilibrium. It has been suggested that the pentose phosphate pathway (PPP) and glycolysis are directly involved in the dynamics and regulation of glioma cell proliferation and migration. The PPP is implicated in cellular redox homeostasis and the modulation of signaling pathways, which play a fundamental role in the progression of tumors to malignant grades, metastasis, and drug resistance. Several studies have shown that in glioblastoma cells, the activity, expression, and metabolic flux of some PPP enzymes increase, leading to heightened activity of the pathway. This generates higher levels of DNA, lipids, cholesterol, and amino acids, favoring rapid cell proliferation. Due to the crucial role played by the PPP in the development of glioma cells, enzymes from this pathway have been proposed as potential therapeutic targets. This review summarizes and highlights the role that the PPP plays in glioma cells and focuses on the key functions of the enzymes and metabolites generated by this pathway, as well as the regulation of the PPP. The studies described in this article enrich the understanding of the PPP as a therapeutic tool in the search for pharmacological targets for the development of a new generation of drugs to treat glioma.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 117-126"},"PeriodicalIF":3.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The substrate preferences and “counting” mode of the cyanobacterial ω3 (Δ15) acyl-lipid desaturase 蓝藻ω3 （Δ15）酰基脂质去饱和酶的底物偏好和计数模式。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-29 DOI: 10.1016/j.biochi.2025.01.009

Alexander Yu. Starikov, Roman A. Sidorov, Georgy V. Kazakov, Pavel A. Leusenko, Dmitry A. Los

{"title":"The substrate preferences and “counting” mode of the cyanobacterial ω3 (Δ15) acyl-lipid desaturase","authors":"Alexander Yu. Starikov, Roman A. Sidorov, Georgy V. Kazakov, Pavel A. Leusenko, Dmitry A. Los","doi":"10.1016/j.biochi.2025.01.009","DOIUrl":"10.1016/j.biochi.2025.01.009","url":null,"abstract":"<div><div>Fatty acid desaturases (FADs) belong to of the oxygenase superfamily. They play important roles in metabolic pathways and adaption mechanisms in a wide range of organisms, including bacteria and humans. These enzymes dehydrogenate a single bond in the acyl chain of fatty acids (FAs), forming a double bond. Multiple parameters influence the precise position of double bond formation and acyl chain docking in the catalytic pocket of various FADs, such as the length of an acyl chain, the position of previously generated double bonds, the location of the enzyme's metal catalytic site, and so on. The “counting” mode differs from one FAD to another. The cyanobacterium <em>Synechocystis</em> sp. strain PCC 6803 has four FADs (Δ9, Δ12, Δ6, and Δ15 or ω3) that synthesize mono-, di-, tri-, and tetraenoic FAs. The substrate preferences and “counting” modes for the first three FADs have been identified, but the substrate specificity for the terminal ω3-FAD remains uncertain. We used molecular cloning, heterologous expression with exogenous FAs, and molecular docking to explore the substrate selectivity and counting mode of ω3-FAD. Our results show that ω3-FAD “counts” from the carboxyl (Δ) end, introduces a double bond between 15 and 16 atoms, and requires a specific acyl substrate configuration with two pre-existing double bonds at Δ<sup>9</sup> and Δ<sup>12</sup> positions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 74-82"},"PeriodicalIF":3.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial dynamics: Molecular mechanism and implications in endometriosis 线粒体动力学：子宫内膜异位症的分子机制和意义。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-28 DOI: 10.1016/j.biochi.2025.01.012

Ylenia Marino , Francesca Inferrera , Tiziana Genovese , Salvatore Cuzzocrea , Roberta Fusco , Rosanna Di Paola

{"title":"Mitochondrial dynamics: Molecular mechanism and implications in endometriosis","authors":"Ylenia Marino , Francesca Inferrera , Tiziana Genovese , Salvatore Cuzzocrea , Roberta Fusco , Rosanna Di Paola","doi":"10.1016/j.biochi.2025.01.012","DOIUrl":"10.1016/j.biochi.2025.01.012","url":null,"abstract":"<div><div>Endometriosis affects about 10 % of women of reproductive age, leading to a disabling gynecologic condition. Chronic pain, inflammation, and oxidative stress have been identified as the molecular pathways involved in the progression of this disease, although its precise etiology remains uncertain. Although mitochondria are considered crucial organelles for cellular activity, their dysfunction has been linked to the development of this disease. The purpose of this review is to examine the functioning of the mitochondrion in endometriosis: in particular, we focused on the mitochondrial dynamics of biogenesis, fusion, and fission. Since excessive mitochondrial activity is reported to affect cell proliferation, we also considered mitophagy as a mechanism involved in limiting disease development. To better understand mitochondrial activity, we also considered alterations in circadian rhythms, the gut microbiome, and estrogen receptors: indeed, these mechanisms are also involved in the development of endometriosis. In addition, we focused on recent research about the impact of numerous substances on mitochondrial activity; some of them may offer a future breakthrough in endometriosis treatment by acting on mitochondria and inhibiting cell proliferation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"231 ","pages":"Pages 163-175"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advanced profiling and structural analysis of anencephaly gangliosides by ion mobility tandem mass spectrometry 离子迁移率串联质谱分析无脑儿神经节苷类的高级谱图和结构分析。

IF 3.3 3区生物学

Biochimie Pub Date : 2025-01-28 DOI: 10.1016/j.biochi.2025.01.011

Maria Roxana Biricioiu , Mirela Sarbu , Raluca Ica , Željka Vukelić , David E. Clemmer , Alina D. Zamfir

{"title":"Advanced profiling and structural analysis of anencephaly gangliosides by ion mobility tandem mass spectrometry","authors":"Maria Roxana Biricioiu , Mirela Sarbu , Raluca Ica , Željka Vukelić , David E. Clemmer , Alina D. Zamfir","doi":"10.1016/j.biochi.2025.01.011","DOIUrl":"10.1016/j.biochi.2025.01.011","url":null,"abstract":"<div><div>Anencephaly, the most severe type of neural tube defects (NTDs) in humans, occurs between the third and fourth gestational weeks (GW), involves the cranial part of the NT and results in the absence of the forebrain and skull. Exposed to amniotic fluid toxicity, neural tissue is degraded and prevented from development. Currently, little is known about the molecular bases of the disease and the possible involvement of glycans. In this context, considering the role played by gangliosides (GGs) in fetal brain development and the previous achievements of ion mobility separation (IMS) mass spectrometry (MS) in biomarker discovery, we report here on the introduction of this advanced analytical technique in NTD research, and its optimization for a comprehensive determination of anencephaly gangliosidome. Three native GG extracts from residual brains of anencephalic fetuses in 28, 35 and 37 GW were comparatively profiled by IMS MS, structurally analyzed by IMS MS/MS, and finally assessed against a native GG mixture from normal fetal brain. IMS MS provided data on 343 anencephaly gangliosides <em>vs</em>. only 157 known before and revealed for the first time the incidence of the entire penta-to octasialylated series. The comparative assay disclosed variations in GG expression with fetal age and a correlation of the pattern with the developmental stage. In contrast to the normal fetal brain, the neural tissue in anencephaly was found to contain an elevated number of polysialogangliosides and a lower expression of <em>O</em>-Ac- and GalNAc-modified glycoforms. These species worth further detailed investigation as new potential anencephaly markers.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 91-104"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0