Cell Biochemistry and Biophysics最新文献

Comparison of Superoxide Dismutase Activity at the Cell, Organ, and Whole-Body Levels.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-07 DOI: 10.1007/s12013-025-01708-3

Sodikdjon A Kodirov

{"title":"Comparison of Superoxide Dismutase Activity at the Cell, Organ, and Whole-Body Levels.","authors":"Sodikdjon A Kodirov","doi":"10.1007/s12013-025-01708-3","DOIUrl":"https://doi.org/10.1007/s12013-025-01708-3","url":null,"abstract":"Superoxide dismutase (SOD) can be considered an antitoxic metalloenzyme that facilitates the production of oxygen and hydrogen peroxide from superoxide anions. Four classes have been identified depending on selective binding of metals, namely Cu,Zn-SOD, Fe-SOD, Mn-SOD, and Ni-SOD. The established isoforms are SOD1, SOD2, and SOD3 in various cells and tissues of eukaryotes. The relatively newer type Ni-SOD binds nickel and is observed in bacteria, including the genus Streptomyces. The Fe-SOD and Mn-SOD are also present in bacteria. Cu,Zn superoxide dismutase (SOD1) activity correlates with various pathophysiological states of organs. SOD2 binds manganese (Mn) and is located in the mitochondria. The SOD3, similar to the SOD1, binds copper and zinc, which are also expressed in the brain. The assay relies on several methods, including the enzyme activities, expression, field potential, and patch-clamp electrophysiology. The effects of SOD activity are emphasized at organ and whole-body levels depending on animal models. The antioxidant properties and behavior of SOD are compared based on responses among females and males to diet and toxic substances. However, in humans with amyotrophic lateral sclerosis (ALS), the mean SOD activity in both erythrocytes and muscles was comparable to controls. The detailed comparisons between the catalase and SOD activities are one of the aspects of this review. Also, modulation of excitability and synaptic plasticity in neurons by SOD is highlighted.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular docking and Enzymatic Inhibition for Therapeutic Potential.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-07 DOI: 10.1007/s12013-025-01740-3

Vagif Farzaliyev, Adem Ertürk, Afat Huseynova, Yeliz Demir, Hatice Kızıltaş, Afsun Sujayev, Mir Ali İsakov, Beyim Ibrahimova, İlhami Gülçin

{"title":"Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular docking and Enzymatic Inhibition for Therapeutic Potential.","authors":"Vagif Farzaliyev, Adem Ertürk, Afat Huseynova, Yeliz Demir, Hatice Kızıltaş, Afsun Sujayev, Mir Ali İsakov, Beyim Ibrahimova, İlhami Gülçin","doi":"10.1007/s12013-025-01740-3","DOIUrl":"https://doi.org/10.1007/s12013-025-01740-3","url":null,"abstract":"In this study, a series of new oxirane and thiirane (2a-g), were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). So, in the first stage, 1-chloro-3-phenothiazylpropanol-2 (2), methyl, methoxy-substituted oxirane, thiirane (2a and 2b), methyl, 1,2-aminopropanethiols (2c-2f), trifluorinated aminethiol derivative (2g), have been synthesized. The structures of synthesized compound were confirmed by IR, NMR analysis. Enzyme inhibition studies demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.21 ± 0.072-12.64 ± 0.12, 5.93 ± 0.028- 81.87 ± 12.52 and 61.43 ± 10.01-344.22 ± 33.87 nM, respectively. Additionally, molecular docking studies were conducted to investigate further the binding interactions of the most potent inhibitors with enzyme active sites, revealing strong hydrogen bonding, π-stacking, and halogen interactions. These findings indicate that the synthesized compounds exhibit high affinity and specificity for the target enzymes, suggesting their potential for further development as therapeutic agents. Future studies will focus on optimizing the structural features of these compounds to enhance their selectivity and bioavailability, conducting in vivo evaluations to assess their pharmacokinetic and pharmacodynamic properties, and exploring their potential applications in the treatment of neurodegenerative and metabolic disorders.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Effects and Mechanisms of the YY1/EGFR Axis on Inflammation and Oxidative Stress in Asthma.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-04 DOI: 10.1007/s12013-025-01737-y

Yue Li, Pengfei Li, Tianci Jiang, Ruhao Wu, Yu Wang, Zhe Cheng

{"title":"The Effects and Mechanisms of the YY1/EGFR Axis on Inflammation and Oxidative Stress in Asthma.","authors":"Yue Li, Pengfei Li, Tianci Jiang, Ruhao Wu, Yu Wang, Zhe Cheng","doi":"10.1007/s12013-025-01737-y","DOIUrl":"https://doi.org/10.1007/s12013-025-01737-y","url":null,"abstract":"To investigate the expression of the transcription factor Yin and Yang 1 (YY1) and the effect of oxidative stress on the upregulation of epidermal growth factor receptor (EGFR) expression in a bronchial epithelial cell line. A bronchial epithelial cell line (BEAS-2B) was stimulated with interleukins (IL-4, IL-13, and IL-17A) to simulate the asthma microenvironment. Total RNA and total protein were extracted from the BEAS-2B cells, and the expression of inflammatory markers (TSLP and IL-25) and YY1/EGFR was determined. EGFR was overexpressed/inhibited in BEAS-2B cells, and changes in cell activity (CCK-8), thioredoxin reductase (TrxR), and malonaldehyde (MDA) expression were identified. EGFR expression was determined after interference with YY1. The binding sites of the YY1 and EGFR promoter regions were predicted by online databases. Precipitation of YY1 in the EGFR promoter region was investigated via a chromatin immunoprecipitation (ChIP) assay. After IL-4, IL-13 and IL-17A were used to stimulate BEAS-2B cells, the expression levels of inflammatory markers (TSLP and IL-25) and EGFR were significantly increased in the asthma cell model. After EGFR was overexpressed, EGFR mRNA and protein expression levels were significantly increased, cell viability was significantly increased, the relative expression level of MDA was significantly increased, and the relative expression level of TrxR was significantly decreased. After the expression of EGFR was disrupted, the EGFR mRNA and protein expression levels were significantly decreased, the cell viability was significantly decreased, the relative expression level of MDA was significantly decreased, and the relative expression level of TrxR was significantly increased. After the expression of YY1 was disrupted, the EGFR mRNA and protein expression levels were significantly decreased, and the results of the ChIP assay suggested that YY1 bound to the EGFR promoter region. The YY1/EGFR axis promotes inflammation and increases oxidative stress in BEAS-2B cells.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

CircARID1B Promotes MPP⁺-Induced Death and Inflammation in Dopaminergic Neurons by Elevating MAVS Through Sequestering miR-143-3p.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-04 DOI: 10.1007/s12013-025-01705-6

Xuejie Zhang, Xuan Shi, Zhining Liu

{"title":"CircARID1B Promotes MPP+-Induced Death and Inflammation in Dopaminergic Neurons by Elevating MAVS Through Sequestering miR-143-3p.","authors":"Xuejie Zhang, Xuan Shi, Zhining Liu","doi":"10.1007/s12013-025-01705-6","DOIUrl":"https://doi.org/10.1007/s12013-025-01705-6","url":null,"abstract":"Increasing evidence has shown the involvement of abnormal circRNA in neurodegenerative disease progression, including Parkinson's disease (PD). Hence, this work focused on probing the function and mechanism of circARID1B on PD progression.1-Methyl-4-phenylpyridinium (MPP+)-induced human dopaminergic SK-N-AS neuroblastoma cell models were used to mimic PD injury in vitro. qRT-PCR and western blotting analyses were used to detect the levels of genes and proteins. Cell death was evaluated by cell counting kit-8 assay, flow cytometry, and lactate dehydrogenase (LDH) activity. Oxidative stress was analyzed by measuring the production of reactive oxygen species (ROS) and superoxide dismutase (SOD). Cell inflammation was determined by ELISA analysis. The binding between miR-143-3p and circARID1B or mitochondrial antiviral signaling protein (MAVS) was analyzed by dual-luciferase reporter and RNA immunoprecipitation assays. A high circARID1B expression was observed in MPP+ treated SK-N-AS cells. Functionally, circARID1B deficiency suppressed MPP+-induced apoptosis, LDH release, oxidative stress and inflammatory response in SK-N-AS cells. Mechanistically, circARID1B bound to miR-143-3p, which was reduced in SK-N-AS cells after MPP+ treatment. Moreover, miR-143-3p inhibition reversed the protective effects of circARID1B silencing on MPP+-treated SK-N-AS cells. Subsequently, we confirmed miR-143-3p directly targeted MAVS. MAVS was increased in SK-N-AS cells after MPP+ treatment. Moreover, MAVS overexpression abolished miR-143-3p up-regulation-induced inhibition of cell apoptosis, LDH release, oxidative stress and inflammation. CircARID1B deficiency suppressed MPP+-induced neural death and inflammation by miR-143-3p/MAVS axis, which may offer an improved understanding of PD progression and be useful for the development of circRNA-based therapy in PD.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Metformin Inhibits the Development of Helicobacter pylori-Associated Gastritis by Regulating the ERK-MMP10-IL-1β Axis.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-04 DOI: 10.1007/s12013-025-01739-w

Wenying Zhu, Qiuxia Li, Min Kang

{"title":"Metformin Inhibits the Development of Helicobacter pylori-Associated Gastritis by Regulating the ERK-MMP10-IL-1β Axis.","authors":"Wenying Zhu, Qiuxia Li, Min Kang","doi":"10.1007/s12013-025-01739-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01739-w","url":null,"abstract":"Helicobacter pylori infection is one of the most common factors inducing gastric mucosal inflammation. Upon infecting gastric epithelial cells, H. pylori generates reactive oxygen species (ROS), which act as inducers of matrix metalloproteinases (MMPs). ROS can regulate MMP gene expression and promote their production through the ERK signaling pathway, with MMP-10 being a primary MMP induced during H. pylori infection. By mediating the remodeling of the gastric epithelial and lamina propria layers, MMP-10 enhances H. pylori colonization and its pro-inflammatory effects. As resistance to eradication therapies has significantly increased, H. pylori eradication rates have continued to decline. We investigated the antioxidant effects of metformin on cell viability, migration, and invasion. The in vitro levels of ROS, MMP-10, and the inflammatory factor IL-1β in H. pylori-infected gastric epithelial cells were assessed to determine whether metformin could alleviate H. pylori-induced inflammation and elucidate its potential mechanisms of action. These findings may provide novel insights into adjunctive therapeutic strategies for the effective clinical eradication of H. pylori infection. The results indicated that H. pylori infection significantly increased ROS production, activating the ERK pathway and upregulating MMP-10 expression, which enhanced cellular invasion and the inflammatory response. Metformin intervention effectively blocked this pathological cascade, significantly reducing ROS levels, MMP-10 expression, and the release of inflammatory cytokines, exerting an inhibitory effect on H. pylori-induced inflammation and demonstrating the potential application of metformin as a therapeutic agent.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

"SERBP1 (Hero45) is a Novel Link with Ischemic Heart Disease Risk: Associations with Coronary Arteries Occlusion, Blood Coagulation and Lipid Profile".

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-03 DOI: 10.1007/s12013-025-01736-z

Vladislav Shilenok, Ksenia Kobzeva, Olga Bushueva

{"title":"\"SERBP1 (Hero45) is a Novel Link with Ischemic Heart Disease Risk: Associations with Coronary Arteries Occlusion, Blood Coagulation and Lipid Profile\".","authors":"Vladislav Shilenok, Ksenia Kobzeva, Olga Bushueva","doi":"10.1007/s12013-025-01736-z","DOIUrl":"https://doi.org/10.1007/s12013-025-01736-z","url":null,"abstract":"Ischemic heart disease (IHD), stemming from coronary atherosclerosis, involves pathological processes in which chaperone proteins play an essential role. SERBP1 (Hero45), an RNA-binding protein, has recently been ascribed to the newly discovered class of Hero proteins with chaperone-like activity, making it particularly relevant in atherosclerosis-related diseases. In this study, 2164 subjects (836 IHD patients and 1328 controls) were genotyped for five common single nucleotide polymorphisms (SNPs) of SERBP1 using probe-based PCR. Here, we report that SNPs of SERBP1 are associated with reduced risk of left coronary artery atherosclerosis: rs4655707 (effect allele [EA] T, OR = 0.63, 95% CI 0.43-0.93, p = 0.02), (EA C, OR = 0.63, 95% CI 0.42-0.95, p = 0.02), rs12561767 (EA G, OR = 0.65, 95% CI 0.45-0.96, p = 0.03), rs6702742 (EA A, OR = 0.63, 95% CI 0.43-0.94, p = 0.02). Additionally, SERBP1 loci are linked to lower coronary artery stenosis (rs1058074), improved blood lipid profiles (rs1058074), and favorable blood coagulation parameters (rs4655707, rs6702742, rs1058074, rs12561767). Together, our study is the first to provide evidence that SERBP1 is involved in lipid metabolism and coagulation regulation, modulating IHD risk.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

RNA Binding Protein IGF2BP3 Rehabilitates Glycolysis of Vascular Endothelial Cells to Protect the ox-LDL-induced Cellular Injury via Stabilizing LDHA mRNA.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-03-30 DOI: 10.1007/s12013-025-01735-0

Xing-Chun Mo, Ping Lu, Qu-Cheng Wei, Xiao-Jing Yang

{"title":"RNA Binding Protein IGF2BP3 Rehabilitates Glycolysis of Vascular Endothelial Cells to Protect the ox-LDL-induced Cellular Injury via Stabilizing LDHA mRNA.","authors":"Xing-Chun Mo, Ping Lu, Qu-Cheng Wei, Xiao-Jing Yang","doi":"10.1007/s12013-025-01735-0","DOIUrl":"https://doi.org/10.1007/s12013-025-01735-0","url":null,"abstract":"Vascular endothelial cells (VECs) dysfunction has been revealed to be a major cause of various cardiovascular diseases. Yet, the precise cellular and molecular mechanisms of VECs injury remain elusive. This study aims to investigate the roles and molecular mechanisms of RNA binding protein IGF2BP3 in vascular endothelial cell injury caused by oxidized low-density lipoprotein (ox-LDL). HUVECs were treated with ox-LDL to induce endothelial cell injury, and the cellular responses to ox-LDL were assessed using cell viability and apoptosis assays. IGF2BP3 was expressed at low levels in vascular tissues from atherosclerosis patients. Treatment with ox-LDL significantly decreased the expression of IGF2BP3 in HUVECs. Overexpression of IGF2BP3 effectively reduced the injury induced by ox-LDL. Glucose metabolism enzymes were significantly downregulated in vascular tissues from atherosclerosis patients and in HUVECs treated with ox-LDL, leading to suppressed glucose metabolism. IGF2BP3 upregulated the glucose metabolism enzyme LDHA to alleviate the injury caused by ox-LDL in HUVECs. Analysis of the LDHA sequence revealed the presence of an IGF2BP3 binding motif in its 3'UTR. Further experiments including RNA pull-down, RNA IP, and RNA stability assays confirmed the specific binding of IGF2BP3 to the 3'UTR region of LDHA, stabilizing its transcripts. Rescue experiments demonstrated that IGF2BP3 mitigated vascular endothelial cell injury by regulating LDHA-mediated glucose metabolism. The outcomes of this study elucidate the protective roles of IGF2BP3 in safeguarding vascular endothelial cells against injury.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

LncRNA BANCR/miR-15a/MAPK1 Induces Apoptosis and Increases Proliferation of Vascular Smooth Muscle Cells in Aortic Dissection by Enhancing MMP2 Expression.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-03-29 DOI: 10.1007/s12013-025-01738-x

Zihe Zheng, Wei Wang, Bo Chen, Ming Huang, Tao Wang, Zheng Xu, Xiaofu Dai

{"title":"LncRNA BANCR/miR-15a/MAPK1 Induces Apoptosis and Increases Proliferation of Vascular Smooth Muscle Cells in Aortic Dissection by Enhancing MMP2 Expression.","authors":"Zihe Zheng, Wei Wang, Bo Chen, Ming Huang, Tao Wang, Zheng Xu, Xiaofu Dai","doi":"10.1007/s12013-025-01738-x","DOIUrl":"https://doi.org/10.1007/s12013-025-01738-x","url":null,"abstract":"Aortic dissection is associated with a high mortality rate, contributing to an unfavorable prognosis. Preventive measures are more effective than therapeutic interventions for aortic dissection. While LncRNA BANCR is recognized as a functional translational regulator in various diseases, its role in aortic dissection remains unexplored. This study aims to elucidate the functions and molecular mechanisms of BANCR in aortic dissection. Vascular smooth muscle cells were isolated from dissected aortic tunica media samples and their phenotypes were compared with those of commercial vascular smooth muscle cells. BANCR expression was modulated via transient transfection (overexpression) and small interfering RNA (knockdown). The involvement of the p38 MAPK pathway was examined using the inhibitor SB202190. The competing endogenous RNA network was validated through a dual luciferase assay. Cellular phenotypes were assessed using the CCK-8 assay, scratch assay, and flow cytometry. BANCR was overexpressed in dissected aortic tissues and isolated vascular smooth muscle cells. MiR-15a-5p exhibited binding affinity to both BANCR and MAPK1. Overexpression of BANCR activated p38 phosphorylation, enhanced cell proliferation and migration, and increased apoptosis. SB202190 mitigated these BANCR-induced phenotypes by inhibiting p38 phosphorylation. Additionally, MMP2 upregulation was linked to BANCR overexpression via the p38 MAPK pathway. Suppression of BANCR expression or inhibition of p38 phosphorylation reduced MMP2 levels, thereby reversing BANCR-induced phenotypes. The LncRNA BANCR/miR-15a-5p/MAPK1 axis forms a ceRNA network that modulates MMP2 expression through the p38 MAPK signaling pathway in vascular smooth muscle cells. BANCR overexpression activates p38 MAPK phosphorylation, leading to enhanced MMP2 expression and subsequent increases in cell proliferation, migration, and apoptosis.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Down-regulation of ATP8B2 in Foam Cells Inhibits Autophagic Flux and ox-LDL Degradation in Atherosclerosis.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-03-28 DOI: 10.1007/s12013-025-01728-z

Xiaodong Miao, Rui Pan, Fei Chang

{"title":"Down-regulation of ATP8B2 in Foam Cells Inhibits Autophagic Flux and ox-LDL Degradation in Atherosclerosis.","authors":"Xiaodong Miao, Rui Pan, Fei Chang","doi":"10.1007/s12013-025-01728-z","DOIUrl":"https://doi.org/10.1007/s12013-025-01728-z","url":null,"abstract":"Our study aims to screen and explore the potential molecular mechanisms of atherosclerosis using a comprehensive research approach combining bioinformatics analysis and molecular biology experiments. Bioinformatics analyses were conducted to screen for key genes with significantly differential expression in atherosclerosis. Subsequently, macrophages and foam cells induced from THP-1 cells were utilized to validate the function of these key genes through siRNA knockdown. Molecular biology experiments encompassed reverse transcription polymerase chain reaction (RT-PCR), Western Blotting, immunofluorescence staining, and JC-1 probe detection of mitochondrial membrane potential. ATP8B2, encoding a P4-ATPase, was significantly downregulated in both plaque tissues and circulating macrophages of atherosclerosis patients. This enzyme influences membrane fusion and other dynamic processes by affecting the asymmetric distribution of phospholipids within the bilayer. Knockdown of ATP8B2 expression significantly inhibited autophagic flux in macrophages, manifested by abnormal accumulation of LC3-II and p62 protein levels. Furthermore, downregulation of ATP8B2 expression significantly inhibited the degradation of oxidized low-density lipoprotein (ox-LDL) by macrophages. Simultaneously, reduced ATP8B2 expression led to decreased mitochondrial membrane potential and mitochondrial dysfunction. Our study unveils for the first time the crucial role of ATP8B2 in atherosclerosis, particularly in maintaining autophagic flux, promoting ox-LDL degradation, and sustaining mitochondrial homeostasis.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Identification of Novel Neuraminidase Inhibitors as Potential Anti-Influenza Agents: Virtual Screening, Molecular Docking, in vitro Validation and Molecular Dynamic Simulation Studies.

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-03-27 DOI: 10.1007/s12013-025-01734-1

Junya Liu, Jinbo Niu, Lihua Xu, Huiru Zhao

{"title":"Identification of Novel Neuraminidase Inhibitors as Potential Anti-Influenza Agents: Virtual Screening, Molecular Docking, in vitro Validation and Molecular Dynamic Simulation Studies.","authors":"Junya Liu, Jinbo Niu, Lihua Xu, Huiru Zhao","doi":"10.1007/s12013-025-01734-1","DOIUrl":"https://doi.org/10.1007/s12013-025-01734-1","url":null,"abstract":"The influenza virus causes approximately hundreds of thousands of deaths annually. Coupled with the emergence of drug resistance, there is an urgent need to develop new drugs for the treatment of influenza. Neuraminidase (NA) has long been recognized as a valid drug target for anti-influenza therapy. Herein, in order to identify potential NA inhibitors with novel structures, we employed a structure-based virtual screening strategy to screen a library containing 1.6 million compounds. Based on XP docking score and free energy calculation results, the three compounds E570-1769, K788-4718, and C071-0424 were selected that may have better binding affinity for the NA protein compared to oseltamivir. Amongst, E570-1769 was identified to be the most potential hit. Docking study showed that E570-1769 bound to NA with a binding energy of -10.3 kcal/mol. Moreover, in silico ADME/T studies demonstrated the druggability of E570-1769 was quite well. Furthermore, in vitro assay demonstrated that E570-1769 inhibited the wild-type and H274Y-muatated NAs with IC50 values of 72.6 μM and 229 μM, respectively. Additionally, molecular dynamic (MD) simulation studies were performed to gain a deep insight into the binding modes of E570-1769 in complex with NA. While less potent than oseltamivir, the novel structure of E570-1769 and promising ADME/T properties indicates it as a promising lead for future research.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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