Bioscience Reports最新文献_第3页

The fluoroquinolone compounds potentiate the antifungal activity of the echinocandins against Aspergillus fumigatus. 氟喹诺酮类化合物增强了棘白菌素对烟曲霉的抗真菌活性。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-02-04 DOI: 10.1042/BSR20250001

Jin-Ju Choi, Suzie Kang, Yoonseo Lee, Dong-Hyun Lee, Yuju Jang, Ja-Il Goo, Yongseok Choi, Dongho Lee, Cheol-Won Yun

{"title":"The fluoroquinolone compounds potentiate the antifungal activity of the echinocandins against Aspergillus fumigatus.","authors":"Jin-Ju Choi, Suzie Kang, Yoonseo Lee, Dong-Hyun Lee, Yuju Jang, Ja-Il Goo, Yongseok Choi, Dongho Lee, Cheol-Won Yun","doi":"10.1042/BSR20250001","DOIUrl":"10.1042/BSR20250001","url":null,"abstract":"The antifungal drugs of the echinocandin family show high efficacy against Aspergillus fumigatus. However, their paradoxical effect, which restores fungal growth at high drug concentrations, and the emergence of resistant strains necessitate improvements. We identified 13 fluoroquinolone compounds from a chemical library containing 10,000 compounds that potentiate the antifungal activity of caspofungin. Among them, NE-E07 significantly enhanced the efficacy of echinocandins against A. fumigatus, including resistant strains, without potentiating other antifungal families like voriconazole or amphotericin B. Specifically, NE-E07 demonstrated a unique ability to potentiate caspofungin's activity against the echinocandin-resistant strain USHM-M0051 isolated from patients. Our experiments revealed that NE-E07, in combination with caspofungin, affected ergosterol biosynthesis in a manner consistent with azole drugs. Docking tests suggest that NE-E07 has a high binding affinity with CYP51, which affects ergosterol biosynthesis similarly to azole drugs. Interestingly, known fluoroquinolones like ciprofloxacin, nalidixic acid, and norfloxacin did not show this potentiating effect, suggesting that NE-E07's unique structure is critical for its activity. Moreover, NE-E07 did not enhance echinocandin activity against Candida albicans or Cryptococcus neoformans, highlighting its specific action against A. fumigatus. In vivo studies demonstrated that co-treatment with NE-E07 and caspofungin increased the survival rate of mice infected with A. fumigatus. This significant improvement in survival underscores the potential clinical relevance of NE-E07 as a co-administered drug with echinocandins for treating fungal infections, particularly those resistant to echinocandins.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999523","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

Palmitoylation and regulation of potassium-dependent sodium/calcium exchangers (NCKX). 棕榈酰化和钾依赖性钠/钙交换剂（NCKX）的调控。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-30 DOI: 10.1042/BSR20241051

Ran Tao, Alan D Robertson, William Fuller, Caglar Gök

引用次数: 0

Does COVID-19 impact the QT interval prolongation? Answers from genetic causal inference. COVID-19是否影响QT间期延长？答案来自基因因果推理。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-30 DOI: 10.1042/BSR20241281

Yongfei Song, Zequn Zheng

{"title":"Does COVID-19 impact the QT interval prolongation? Answers from genetic causal inference.","authors":"Yongfei Song, Zequn Zheng","doi":"10.1042/BSR20241281","DOIUrl":"10.1042/BSR20241281","url":null,"abstract":"During the COVID-19 pandemic, there has been heightened interest in the QT interval, a crucial indicator of ventricular electrical activity. Mendelian randomization (MR) is used here to investigate the genetic causation between QT interval alterations and COVID-19. Genetic proxies representing three COVID-19 phenotypes-severe, hospitalized, and COVID-19-were identified in over 1,000,000 individuals of European ancestry. Univariate two-sample MR (TSMR) and multi-exposure-adjusted multivariate MR (MVMR) were used to assess genetic causal associations between COVID-19 and QT intervals in 84,630 UK Biobank participants. The MR-robust adjusted profile score (MR-RAPS) method and radial MR frame were utilized for effective robustness and outlier variant detection, with sensitivity analyses conducted to identify horizontal pleiotropy. For every COVID-19 phenotype, univariate TSMR analysis revealed non-significant causal estimates between COVID-19 and the QT interval [COVID-19: βIVW (95% CI): -0.44 (-1.72, 0.84), P = 0.50; hospitalization: βIVW: 0.12 (-0.57, 0.80), P = 0.74; severe case: βIVW: 0.11 (-0.29, 0.51), P = 0.58]. MR-RAPS and outlier-corrected radial MR analyses further supported this null causal estimation. In confounder-adjusted MVMR analysis, this nonsignificant causality was independent of body mass index (BMI), smoking, and alcohol consumption [βBMI+Alcohol+Smoking (95% CI): -0.77 (-2.44, 0.91), P = 0.37]. Sensitivity analyses did not detect any evidence of bias from horizontal pleiotropy, abnormal data distribution, or weak instruments. These findings suggest that COVID-19 does not directly causally prolong the QT interval. Inconsistent findings in observational research may be attributed to residual confounding.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":"1-14"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799353","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

Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery. 循环、修复、恢复：自噬在调节骨骼肌修复和运动后恢复中的作用。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-30 DOI: 10.1042/BSR20240137

Jordan Acheson, Sophie Joanisse, Craig Sale, Nathan Hodson

{"title":"Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.","authors":"Jordan Acheson, Sophie Joanisse, Craig Sale, Nathan Hodson","doi":"10.1042/BSR20240137","DOIUrl":"10.1042/BSR20240137","url":null,"abstract":"Skeletal muscle is a highly plastic tissue that can adapt relatively rapidly to a range of stimuli. In response to novel mechanical loading, e.g. unaccustomed resistance exercise, myofibers are disrupted and undergo a period of ultrastructural remodeling to regain full physiological function, normally within 7 days. The mechanisms that underpin this remodeling are believed to be a combination of cellular processes including ubiquitin-proteasome/calpain-mediated degradation, immune cell infiltration, and satellite cell proliferation/differentiation. A relatively understudied system that has the potential to be a significant contributing mechanism to repair and recovery is the autophagolysosomal system, an intracellular process that degrades damaged and redundant cellular components to provide constituent metabolites for the resynthesis of new organelles and cellular structures. This review summarizes our current understanding of the autophagolysosomal system in the context of skeletal muscle repair and recovery. In addition, we also provide hypothetical models of how this system may interact with other processes involved in skeletal muscle remodeling and provide avenues for future research to improve our understanding of autophagy in human skeletal muscle.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":"1-30"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817040","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

Insights into heme degradation and hydrogen peroxide-induced dimerization of human neuroglobin. 血红素降解和过氧化氢诱导的人类神经红蛋白二聚化的见解。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-30 DOI: 10.1042/BSR20241265

Alice Cassiani, Paul G Furtmüller, Marco Borsari, Gianantonio Battistuzzi, Stefan Hofbauer

{"title":"Insights into heme degradation and hydrogen peroxide-induced dimerization of human neuroglobin.","authors":"Alice Cassiani, Paul G Furtmüller, Marco Borsari, Gianantonio Battistuzzi, Stefan Hofbauer","doi":"10.1042/BSR20241265","DOIUrl":"10.1042/BSR20241265","url":null,"abstract":"In this present study, we investigated the H2O2-induced oligomerization of wild-type human neuroglobin (hNgb) and of some selected variants (C46AC55A, Y44A, Y44F, Y44AC46AC55A, Y44AC46AC55A) to clarify how the process is affected by the Cys46/Cys55 disulfide bond and the distal H-bonding network and to figure out the molecular determinants of the H2O2-induced formation of amyloid-type structures and hNgb aggregates. It turns out that hydrogen peroxide exerts a two-fold effect on hNgb, inducing both heme breakdown and protein dimerization/polymerization. The enhanced resistance to the oxidizing effect of H2O2 of the disulfide-free variants indicates that both effects are strictly influenced by the heme accessibility for H2O2. Most importantly, the H2O2-induced neuroglobin dimerization/polymerization turns out to be triggered by tyrosyl radicals resulting from the oxidizing action of Compound I ([Por•Fe(IV) = O]+). Peptide mapping indicates that the H2O2-induced dimerization/polymerization of hNgb mainly involves Tyr44, which forms covalent bonds with all the other tyrosine residues, with a minor contribution from Tyr88. The presented findings contribute further important pieces of information in the quest of identifying all capabilities of hNgb and ultimately its physiological task.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":"1-13"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779171","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

Electron transfer in multicentre redox proteins: from fundamentals to extracellular electron transfer. 多中心氧化还原蛋白中的电子转移：从基本原理到细胞外电子转移。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-30 DOI: 10.1042/BSR20240576

Büşra Bayar, Ricardo Soares, Haris Nalakath, Alexandra Alves, Catarina M Paquete, Ricardo O Louro

{"title":"Electron transfer in multicentre redox proteins: from fundamentals to extracellular electron transfer.","authors":"Büşra Bayar, Ricardo Soares, Haris Nalakath, Alexandra Alves, Catarina M Paquete, Ricardo O Louro","doi":"10.1042/BSR20240576","DOIUrl":"10.1042/BSR20240576","url":null,"abstract":"Multicentre redox proteins participate in diverse metabolic processes, such as redox shuttling, multielectron catalysis, or long-distance electron conduction. The detail in which these processes can be analysed depends on the capacity of experimental methods to discriminate the multiple microstates that can be populated while the protein changes from the fully reduced to the fully oxidized state. The population of each state depends on the redox potential of the individual centres and on the magnitude of the interactions between the individual redox centres and their neighbours. It also depends on the interactions with binding sites for other ligands, such as protons, giving origin to the redox-Bohr effect. Modelling strategies that match the capacity of experimental methods to discriminate the contributions of individual centres are presented. These models provide thermodynamic and kinetic characterization of multicentre redox proteins. The current state of the art in the characterization of multicentre redox proteins is illustrated using the case of multiheme cytochromes involved in the process of extracellular electron transfer. In this new frontier of biological electron transfer, which can extend over distances that exceed the size of the individual multicentre redox proteins by orders of magnitude, current experimental data are still unable, in most cases, to provide discrimination between incoherent conduction by heme orbitals and coherent band conduction.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":"1-18"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876057","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

Integrative metabolome and transcriptome analyses provide insights into PHGDH in colon cancer organoids. 代谢组和转录组的综合分析为了解结肠癌有机体中的 PHGDH 提供了线索。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-28 DOI: 10.1042/BSR20240842

Lin Chen, Zhihui Dai, Yanfei Zhang, Huichao Sheng, Bin Hu, Jinlin Du, Jie Chang, Wenxia Xu, Yuqing Hu

{"title":"Integrative metabolome and transcriptome analyses provide insights into PHGDH in colon cancer organoids.","authors":"Lin Chen, Zhihui Dai, Yanfei Zhang, Huichao Sheng, Bin Hu, Jinlin Du, Jie Chang, Wenxia Xu, Yuqing Hu","doi":"10.1042/BSR20240842","DOIUrl":"10.1042/BSR20240842","url":null,"abstract":"As a rate-limiting enzyme in the endogenous serine de novo synthesis pathway, 3-Phosphoglycerate dehydrogenase (PHGDH) has been widely concerned about its role in a variety of tumors including colon cancer and the development of inhibitors. In our previous study, we studied PHGDH in colon cancer cell lines. However, with the development of personalized therapy, we realized that in scientific research, two-dimensional cell lines lost a lot of original characteristic information during long-term culture, and the results obtained may not be enough to support the conclusion. Patient-derived tumor organoids maintain genomic stability and make up for information missing from cell lines due to monoclonal growth. Therefore, in our study, a colon cancer organoid with high PHGDH expression was selected and analyzed for transcriptomic and metabolomic changes through targeted inhibition of PHGDH. The results showed that inhibition of PHGDH significantly inhibited the proliferation of colon cancer organoids. The transcriptome, metabolome, and combined omics analysis showed that the changes in colon cancer organoids after inhibition of PHGDH were mainly involved in PRSS1 and PRSS56, steroid hormone biosynthesis, phenylalanine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. In our study, the role of PHGDH in serine metabolism in colon cancer organoids was clarified by multi-omics analysis to provide new knowledge for an in-depth understanding of serine metabolism and PHGDH function in colon cancer.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":"1-12"},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817038","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

Exploration of vitamin D hydroxy metabolites C3 epimers in patients with cardiovascular disease: an observational study. 心血管疾病患者维生素D羟基代谢物C3外显子的探索：一项观察性研究

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2025-01-27 DOI: 10.1042/BSR20241558

Mohamed Abouzid, Łukasz Kruszyna, Julia Kerner, Leonid Kagan, Aniceta Mikulska-Sauermann, Dorota Filipowicz, Matylda Resztak, Franciszek Krzysztof Główka, Marta Karaźniewicz-Łada

{"title":"Exploration of vitamin D hydroxy metabolites C3 epimers in patients with cardiovascular disease: an observational study.","authors":"Mohamed Abouzid, Łukasz Kruszyna, Julia Kerner, Leonid Kagan, Aniceta Mikulska-Sauermann, Dorota Filipowicz, Matylda Resztak, Franciszek Krzysztof Główka, Marta Karaźniewicz-Łada","doi":"10.1042/BSR20241558","DOIUrl":"10.1042/BSR20241558","url":null,"abstract":"Roughly 90% of the Polish population experiences vitamin D deficiency. The 3-epi-25(OH)D2 and 3-epi-25(OH)D3 are stereoisomers of 25(OH)D2 and 25(OH)D3, and they can inadvertently be included in measurements of 25(OH)D levels, potentially leading to its overestimating. We aimed to measure 25(OH)D2 and 25(OH)D3, their epimers 3-epi-25(OH)D2 and 3-epi-25(OH)D3, and biologically active 1,25(OH)2D3 in patients with cardiovascular disease and healthy volunteers. We enrolled 27 adult patients with cardiovascular disease (64 ± 15 years) and 35 healthy volunteers (36.37 ± 12.29 years). We used a validated ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) method to measure 25(OH)D2/3 concentrations and their epimers. Plasma concentrations of 1α,25(OH)2D3 were determined by sensitive and quantitative enzyme immunoassay following intra- and inter-day validation. Vitamin D insufficiency was observed in approximately 52% of the patients and 37% of healthy volunteers. Comparable levels of 25(OH)D3 and 25(OH)D2 were seen in both groups. The observed levels of the epimeric form 3-epi-25(OH)D3 appeared approximately 1.7 times higher in healthy volunteers, accounting for 9% misclassified according to vitamin D status. Also, patients had lower concentrations of 1,25(OH)2D3, and their 3-epi-25(OH)D2 levels were below the detection limit (2 ng/mL). In all studied subjects, 25(OH)D3 was negatively correlated with % 3-epi-25(OH)D3 (R=-0.758; P<0.001), and 3-epi-25(OH)D2 was negatively correlated with % 3-epi-25(OH)D2 (R = -0.842; P = 0.002). While the mechanism of how vitamin D epimeric forms influence diseases remains unclear, we recommend maintaining 25(OH)D3 levels above 20 ng/mL.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051025","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

Transcriptional profiling reveals the role of Candida albicans Rap1 in oxidative stress response. 转录谱分析揭示了白色念珠菌 Rap1 在氧化应激反应中的作用。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2024-12-17 DOI: 10.1042/BSR20240689

Wen-Han Wang, Hsuan-Yu Chen, Sheng-Yuan Chen, Chung-Yu Lan

{"title":"Transcriptional profiling reveals the role of Candida albicans Rap1 in oxidative stress response.","authors":"Wen-Han Wang, Hsuan-Yu Chen, Sheng-Yuan Chen, Chung-Yu Lan","doi":"10.1042/BSR20240689","DOIUrl":"10.1042/BSR20240689","url":null,"abstract":"Candida albicans is a member of the human commensal microbiota but can also cause opportunistic infections, including life-threatening invasive candidiasis, particularly in immunocompromised patients. One of the important features of C. albicans commensalism and virulence is its ability to adapt to diverse environmental stress conditions within the host. Rap1 is a DNA-binding protein identified in yeasts, protozoa, and mammalian cells, and it plays multiple functions, including telomere regulation. Intriguingly, our previous study showed that Rap1 is also involved in cell wall integrity, biofilm formation, and virulence in C. albicans. In this work, using RNA-seq analysis and other approaches, the role of C. albicans Rap1 in oxidative stress response was further revealed. The RAP1-deletion mutant exhibited greater resistance to the superoxide generator menadione, a lower level of intracellular reactive oxygen species (ROS) upon menadione treatment, and higher expression levels of superoxide dismutase genes, all in response to oxidative stress. Moreover, the association between Rap1-mediated oxidative stress response and the mitogen-activated protein kinase (MAPK) Hog1, the transcription factor Cap1 and the TOR signalling was also determined. Together, these findings expand our understanding of the complex signalling and transcriptional mechanisms regulating stress responses in C. albicans.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685885","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 physiological anti-hypertensive peptide catestatin and its common human variant Gly364Ser: differential cardiovascular effects in a rat model of hypertension. 生理性抗高血压肽 catestatin 及其常见人类变体 Gly364Ser：在高血压大鼠模型中的不同心血管效应。

IF 3.8 3区生物学

Bioscience Reports Pub Date : 2024-12-17 DOI: 10.1042/BSR20241433

Jitesh Singh Rathee, Dhanya R Iyer, Malapaka Kiranmayi, Samarasimha Reddy, V V Sureshbabu, Nitish R Mahapatra

{"title":"The physiological anti-hypertensive peptide catestatin and its common human variant Gly364Ser: differential cardiovascular effects in a rat model of hypertension.","authors":"Jitesh Singh Rathee, Dhanya R Iyer, Malapaka Kiranmayi, Samarasimha Reddy, V V Sureshbabu, Nitish R Mahapatra","doi":"10.1042/BSR20241433","DOIUrl":"10.1042/BSR20241433","url":null,"abstract":"Catestatin (CST), a 21-amino acids physiological peptide, has emerged as a key modulator of cardiovascular functions due to its anti-hypertensive and cardioprotective properties. However, the ramifications of the most common human variant of CST (viz., Gly364Ser) on cardiovascular pathophysiology remain partially understood. In this study, hypertension was induced in uninephrectomized rats by treatment with deoxycorticosterone-acetate and sodium chloride (DOCA-salt). The DOCA-salt-induced hypertensive (DSHR) animals were then intraperitoneally administered with either CST wild-type (CST-WT) or 364Ser variant (CST-Ser) peptide. CST-Ser was profoundly less effective than CST-WT in rescuing the elevated systolic blood pressure [from ∼211 mmHg to ∼176 mmHg, p < 0.0001 (CST-Ser) versus ∼116 mmHg, p < 0.0001 (CST-WT)] and heart rate [from ∼356 bpm to ∼314 bpm, p = 0.66 (CST-Ser) versus ∼276 bpm, p = 0.02 (CST-WT)]. CST-Ser also showed diminished effects in lowering diastolic blood pressure and mean arterial pressure in the DSHR animals. Furthermore, CST-Ser was inefficient/markedly less potent in rescuing the impaired contractile and diastolic function in DSHR animals [improvements in the contractility index by ∼22 s-1 (CST-Ser), p = 0.15 versus by ∼84 s-1 (CST-WT), p < 0.0001 and decrease in end-diastolic pressure by ∼4 mmHg (CST-Ser), p = 0.015 versus by ∼14 mmHg (CST-WT), p < 0.0001]. Moreover, CST-Ser exerted less potent anti-inflammatory effects on the DSHR hearts than CST-WT. These findings are in concordance with the elevated systolic/diastolic blood pressure observed in Ser variant carriers from various human populations. This study provides compelling evidence for the diminished anti-hypertensive and cardioprotective effects of the CST-Gly364Ser variant.","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709020","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