Biochemical Genetics最新文献

{"title":"Genetic Diversity and Drought Stress Tolerance of a Global Collection of Pearl Millet at Germination and Early Seedling Growth Stages.","authors":"Haitham Saleh, Abdelfattah Badr, Ehab M Zayed, Elham R S Soliman","doi":"10.1007/s10528-024-10965-5","DOIUrl":"https://doi.org/10.1007/s10528-024-10965-5","url":null,"abstract":"<p><p>Pearl millet {Pennisetum glaucum (L.) R. Br} is a C4 panicoid cereal millet crop grown in arid and semi-arid regions in Africa and Asia for food and fodder. This study involves the evaluation of the genetic diversity of 28 worldwide germplasm collection of pearl millet by genetic markers polymorphism and drought tolerance indices. The genetic diversity was expressed by 51 alleles of 9 ISSR markers that showed 96.43% total polymorphism and 11.76 alleles per marker. Cluster analysis of ISSR markers polymorphism divided the 28 genotypes into four clusters partially in agreement with their origin. The application of drought stress simulated by 20% PEG₆₀₀₀ treatment, retarded the germination percentage, and reduced shoot and root length, seedling fresh and dry weights. Drought tolerance indices (DTIs) were calculated based on the response of the seedling traits under drought stress compared to the control seedlings. ANOVA revealed statistically significant variation among the genotypes (P ≤ 0.05), except for seedling fresh weight (P = 0.17 > 0.05) under control conditions and seedling dry weight (P = 0.99 > 0.05) under drought conditions. Genotypes having higher DTIs for three traits are regarded drought resistant, i.e., those from India, Ethiopia, Pakistan, and Nigeria. The calculated heritability values indicated that seedlings dry weight is the least trait affected by drought stress whereas root length is the most influenced trait. Hierarchical clustering, based on the DTI values, also grouped the genotypes partially concomitant to their origin. The correlation analysis demonstrated a modest positive correlation between shoot length and root length. A low correlation of r ≤ 0.12 was observed between the morphological DTI matrix and the genetic matrix. Nevertheless, high levels of genetic diversity were identified among the examined genotypes that may face genetic erosion by climatic constraints, and a high potential for creating agronomically superior cultivars by crossing widely divergent genotypes.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876002","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}

{"title":"Impact of rs2046045 SNP in PDE8B on TSH Levels: Insights into Genetic Susceptibility to Hypothyroidism.","authors":"Salim Khan, Nikki Rani, Anita Yadav, Ranjan Gupta","doi":"10.1007/s10528-024-11005-y","DOIUrl":"https://doi.org/10.1007/s10528-024-11005-y","url":null,"abstract":"<p><p>Hypothyroidism is the most prevalent thyroid disorder and leads to adverse effects on the human body. Serum thyroid stimulating hormone (TSH) values have been related to polymorphisms in multiple genes that may be involved in the regulation of thyroid function. The single nucleotide polymorphism (SNP) rs2046045 is situated in the intron region of the phosphodiesterase 8B (PDE8B) gene, which encodes a high-affinity cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase widely expressed in thyroid tissue. The principal goal of the present study was to investigate the association between the SNP rs2046045 of the PDE8B gene and hypothyroidism. The study was designed as a case-control study, and a total of 160 hypothyroid and 160 healthy controls were involved. Blood samples were drawn from each individual, and deoxyribonuleic acid (DNA) was separated with a suitable DNA isolation kit. For genotyping, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed. The IBM Statistical Package for Social Sciences (SPSS) 25.0 was utilized to analyze the statistical data. Age differences between the patients and controls were not observed in the present study. The genotype frequency of homozygous wild type (TT), homozygous mutate type (GG), and heterozygous (GT) was 45%, 2.5%, and 52.5%, respectively, in control subjects and 27.5%, 11.25%, and 61.25%, respectively, in cases, and showed a significant difference (p = 0.0002). The minor G allele frequency is elevated in hypothyroid patients as compared to healthy control subjects (41.87% vs. 28.75%), p = 0.0005. The presence of the mutant allele G of rs2046045 in the PDE8B gene correlates with elevated serum TSH levels in hypothyroid patients.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871021","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}

{"title":"LncRNA SNHG16 Drives PD-L1-Mediated Immune Escape in Colorectal Cancer through Regulating miR-324-3p/ELK4 Signaling.","authors":"Zhiyuan Chen, Zhenjuan Wu, Minghao Wu, Yu Zhang, Sha Hou, Xiangyang Wang, Ya Peng","doi":"10.1007/s10528-024-11000-3","DOIUrl":"https://doi.org/10.1007/s10528-024-11000-3","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a common malignancy that claims the life of many patients. Nucleolar RNA host gene 16 (SNHG16) has been identified as an oncogene in CRC development. However, the role and mechanism of SNHG16 in CRC remain unclear. A total of 27 cases of CRC tumor tissues and adjacent tissues were collected to investigate the expression and correlation among SNHG16, miR-324-3p, ELK4 and PD-L1 using qRT-PCR, western blot and Pearson analysis. Cell proliferation, migration and invasion abilities were determined using CCK-8 and transwell assays. The cytotoxicity of CD8 + T cells and the apoptosis of CD8⁺ T cells was evaluated by LDH assay and flow cytometry, respectively. Dual luciferase assay, RIP and ChIP methods were performed to verify molecular interactions. Our results showed that SNHG16, ELK4 and PD-L1 expression were abnormally elevated and miR-324-3p expression was decreased in tumor tissues from CRC patients and CRC cells. SNHG16 silencing resulted in suppression of cell growth, metastasis, and immune escape of CRC cells, which was reversed by miR-324-3p inhibitor and ELK4 overexpression. Mechanistically, SNHG16 acted as a competitive endogenous RNA to enhance ELK4 expression by sponging miR-324-3p, thereby provoking the transcription of PD-L1. Our results demonstrated that SNHG16 silencing led to the suppression of cell growth, metastasis, and immune escape of CRC cells through mediating miR-324-3p/ELK4/PD-L1 axis, offering promising targets for CRC treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833597","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}

{"title":"Let-7c-5p Targeting CHD7 Hinders Cervical Cancer Migration and Invasion by Regulating Cell Adhesion.","authors":"Huichuan Zhao, Lanying Zou, Jun Xu, Xiaoping Zhou, Ya Zhang","doi":"10.1007/s10528-024-10993-1","DOIUrl":"10.1007/s10528-024-10993-1","url":null,"abstract":"<p><p>Cervical cancer is one of the most common cancers worldwide. Many studies have reported the involvement of various miRNAs in cervical cancer progression. Our study was centered at investigating how let-7c-5p affected cervical cancer migration and invasion by regulating cell adhesion and its molecular mechanism. Bioinformatics was used for the analysis on differentially expressed mRNAs in cervical cancer and the prediction of their upstream regulatory miRNAs. Immunohistochemistry was performed to assess the expression of CHD7 in cervical cancer tissue. qRT-PCR was performed for examining how much let-7c-5p and CHD7 were expressed. Dual-luciferase assay was performed to verify the regulatory relationship between CHD7 and let-7c-5p. The CCK-8 and transwell assays helped in detecting cell viability, invasion and migration. The ability by which cells adhered to each other was detected by employing cell adhesion assay. In addition, the expression levels of the proteins related to cell adhesion and CHD7 were detected by Western blot. A remarkable high expression-level of CHD7 was discovered in cervical cancer tissues and cells. The cell viability, migration and invasiveness could be suppressed by the knockdown of CHD7 which could also attenuate the expression of cell adhesion-related proteins. Bioinformatics analysis showed that CHD7 had an upstream regulatory gene, miRNA-let-7c-5p, which was markedly lowly expressed in cervical cancer tissues and cells. To validate the binding relationship between CHD7 and let-7c-5p, dual-luciferase assay was performed. Rescue experiments revealed that the cancer-inhibiting effect of let-7c-5p in cervical cancer could be reversed by overexpressed CHD7. let-7c-5p regulates cell adhesion and attenuates cervical cancer migration and invasiveness by targeting CHD7. It indicates that the involvement of let-7c-5p/CHD7 axis is of significance in cervical cancer progression, which opens up new possibilities for us to develop novel clinical treatments for cervical cancer.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826737","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}

{"title":"METTL3-Mediated m6A Methylation of USP21 Contributes to Hepatocellular Carcinoma Progression by Stabilizing H2BFS Through Deubiquitination.","authors":"Peng Yao, Xiaozheng Li, Jiasui Chai, Jiejie Dong, Yan Chen, Tong Zhang, Xingren Guo","doi":"10.1007/s10528-024-10992-2","DOIUrl":"10.1007/s10528-024-10992-2","url":null,"abstract":"<p><p>Deubiquitinases play essential roles in hepatocellular carcinoma (HCC) progression, however, the role of ubiquitin-specific peptidase 21 (USP21) in HCC development remains unclear. The present work aims to analyze the effect of USP21 on tumor property of HCC cells and the underlying mechanism. mRNA expression levels of USP21 and H2BFS were analyzed by quantitative real-time polymerase chain reaction. Protein expression of USP21, E-cadherin, N-cadherin, Vimentin, H2BFS and methyltransferase 3 (METTL3) was assessed by western blotting assay or immunohistochemistry assay. Clonogenicity assay was used to analyze cell proliferation. Flow cytometry assay was performed to quantify apoptotic rate of cells. Wound-healing assay and transwell assay were conducted to analyze cell migration and invasion, respectively. Xenograft mouse model assay was performed to determine the effect of USP21 knockdown on tumor formation. m6A RNA immunoprecipitation assay (MeRIP) was used to analyze the effect of METTL3 silencing on methylated level of USP21. USP21 expression was upregulated in HCC tissues and cells when compared with control groups. USP21 silencing inhibited proliferation, migration and invasion and induced apoptosis of HCC cells, accompanied by the increased E-cadherin protein expression and decreased N-cadherin and Vimentin protein expression. Moreover, USP21 knockdown delayed tumor formation in vivo. USP21 stabilized H2BFS by deubiquitination, and H2BFS overexpression attenuated USP21 silencing-induced effects in HCC cells. Further, METTL3-mediated m6A methylation of USP21. METTL3-mediated m6A methylation of USP21 promoted HCC progression by stabilizing H2BFS through deubiquitination.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826791","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}

{"title":"The Expression of SIRT3 in Endometrial Carcinoma and Its Effect on Promoting Apoptosis of Ishikawa Cells.","authors":"Xinyu Zhao, Xuebei Yin","doi":"10.1007/s10528-024-10995-z","DOIUrl":"https://doi.org/10.1007/s10528-024-10995-z","url":null,"abstract":"<p><p>Endometrial cancer (EC) is one of the three most common malignancies of the female reproductive system. SIRT3 is an NAD+-dependent protein deacetylase that maintains the stability of the intracellular environment. This study aims to investigate the mechanism of SIRT3 in regulating apoptosis in endometrial cancer and further reveal the role of SIRT3 in endometrial cancer. Differential expression of SIRT3 in tumors was analyzed by GEPIA using TCGA database data. Meanwhile, mRNA and protein expression levels of SIRT3 in tissues and cells were examined using RT-qPCR, Western Blot, and immunohistochemistry. The expression of SIRT3 after estradiol (E2) stimulation of Ishikawa cells was detected using RT-qPCR and Western Blot techniques. The effect of transfection after SIRT3 knockdown and overexpression was verified using RT-qPCR and Western Blot. Flow cytometry and TUNEL assay were used to detect the effect of SIRT3 on apoptosis. Reactive oxygen species (ROS) was used to detect the effect of SIRT3 on the level of oxidative stress in cells. The expression of apoptotic protein (BAX, cleaved-Caspase 3) and autophagy protein (cyto C and LC3A) were detected in transfected Ishikawa cell. Differences analysis of TCGA database data showed that the expression of SIRT3 in EC was significantly lower than that in normal endometrial tissue. The mRNA and protein levels of SIRT3 were significantly lower in EC tissues or cells than normal controls. E2 stimulation in Ishikawa cells resulted in the down-regulation of SIRT3 expression. After transfection, SIRT3 promoted the apoptosis of Ishikawa cells and attenuated the levels of ROS. Overexpression of SIRT3 promoted apoptosis and autophagy-related proteins. Thus, high expression of SIRT3 inhibits the development of EC whereas low expression of SIRT3 may promote the progression of EC, which provides a new direction for studying the treatment of EC.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816868","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}

{"title":"FNDC1 Facilitates Proliferation, Migration, and Invasion of Breast Cancer Cells Through Modulating Wnt/β-Catenin Pathway.","authors":"Guocai Fan, Chen Zhang","doi":"10.1007/s10528-024-10994-0","DOIUrl":"https://doi.org/10.1007/s10528-024-10994-0","url":null,"abstract":"<p><p>Breast cancer is the most common malignant cancer and the leading fatal cancer in women around the world. Fibronectin type III domain-containing protein 1 (FNDC1) has been demonstrated to play crucial roles in various tumors. However, the function of FNDC1 in breast cancer remains to be addressed. Increased FNDC1 expression was found in breast cancer that is associated with individual cancer stages and lymph node metastasis through UALCAN analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays indicated that FNDC1 expression was up-regulated in breast cancer cells. The results of Cell Counting Kit-8 and colony formation assays indicated that FNDC1 promoted the proliferation of breast cancer cells. Moreover, FNDC1 knockdown suppressed xenograft tumor growth and inhibited the levels of FNDC1 and marker of proliferation Ki-67. Transwell assay demonstrated that FNDC1 promoted the migration and invasion of breast cancer cells. Importantly, mechanism analysis implied that FNDC1 promoted the Wnt/β-catenin signaling pathway. Notably, Wnt/β-catenin activation with LiCl significantly enhanced the proliferation and epithelial-mesenchymal transformation (EMT) inhibition effect of silencing FNDC1, whereas Wnt/β-catenin inhibition with XAV-939 significantly weakened the proliferation and EMT promotion effect of FNDC1. Analysis of β-catenin expression in the nucleus and cytoplasm showed that FNDC1 promoted β-catenin nuclear translocation. These data suggested that FNDC1 exerts its oncogene function through modulating Wnt/β-catenin signaling pathway. In conclusion, FNDC1 promotes cell proliferation, migration, invasion, and EMT through modulating Wnt/β-catenin signaling pathway in breast cancer, providing a new idea for the development of breast cancer therapeutic targets.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816909","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}

{"title":"ETS1 Promotes Aerobic Glycolysis and Growth in Head and Neck Squamous Cell Carcinoma by Targeting RRAS2.","authors":"Jianguo Liu, Zhi Wang, Xiaoyan Tian, Bingbin Xie, Ke Liu","doi":"10.1007/s10528-024-10996-y","DOIUrl":"https://doi.org/10.1007/s10528-024-10996-y","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with a five-year survival rate below 50%, highlighting the urgent need for novel therapeutic targets. This study explores the role of the small GTPase RRAS2 in HNSCC progression and its regulation of glycolysis. Analysis of data from the TCGA and GTEx databases revealed that RRAS2 is significantly upregulated in HNSCC tissues and is associated with poorer overall patient survival. Functional experiments demonstrated that silencing RRAS2 in HNSCC cell lines inhibits glycolytic activity and cell proliferation while promoting apoptosis, whereas overexpression of RRAS2 enhances glycolysis and cell growth. Additionally, bioinformatics and experimental approaches identified the transcription factor ETS1 as an upstream regulator of RRAS2. ETS1 binds to the RRAS2 promoter, facilitating its transcription and contributing to metabolic reprogramming in HNSCC cells. Rescue experiments confirmed that the ETS1-RRAS2 axis is crucial for maintaining the glycolytic phenotype and proliferative capacity of HNSCC cells. These findings suggest that the ETS1-RRAS2 pathway plays a critical role in HNSCC progression and metabolic adaptation, positioning RRAS2 as a potential therapeutic target for improving patient outcomes.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805696","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}

{"title":"Reduced Expression of Oxidative Stress-Related lncRNAs LINC-PINT and SNHG5 in Schizophrenia: Implications for Biomarker Development.","authors":"Vahid Amirhassani, Bashdar Mahmud Hussen, Solat Eslami, Arezou Sayad, Soudeh Ghafouri-Fard","doi":"10.1007/s10528-024-10986-0","DOIUrl":"https://doi.org/10.1007/s10528-024-10986-0","url":null,"abstract":"<p><p>Schizophrenia is a mental condition that impairs several aspects of brain function and behavior. Recent investigations highlighted abnormal function of numerous genes in this context. Notably, genes that affect oxidative stress and neuron damage were the focus of several studies. In an attempt to find a biomarker that can be quantified in the peripheral blood, we assessed blood expression of three lncRNAs that were associated with these processes in patients with schizophrenia and matched controls. We observed a statistically significant downregulation of SNHG5 in the patient group compared to healthy controls, with P-values of < 0.0001, 0.0008, and 0.003 in total, male, and female patients, respectively. LINC-PINT was also found to be down-regulated in all comparisons between patients and controls with P-values of < 0.0001, < 0.0001 and = 0.01, in total, male, and female patients, respectively. However, statistical analyses disclosed no notable difference in the expression of TP53TG1 between study subgroups. Most notably, LINC-PINT and SNHG5 could discriminate between patients and controls with acceptable AUC and specificity values. Cumulatively, the results of this study propose down-regulation of LINC-PINT and SNHG5 as a possible peripheral indicator of the presence of schizophrenia.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798920","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}

{"title":"Inflammatory Signaling Induces Mitochondrial Dysfunction and Neuronal Death in Traumatic Brain Injury via Downregulation of OXPHOS Genes.","authors":"Hui Dong, Hui Zhang, Lei Cai, Quanyi Ye, Heping Wang, Bo Liu, Wenhu Zhang, Junxin Li","doi":"10.1007/s10528-024-10980-6","DOIUrl":"https://doi.org/10.1007/s10528-024-10980-6","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a major cause of neurological dysfunction and disability. This study aimed to investigate the transcriptomic changes and the functional consequences in TBI, focusing on the interplay between inflammation and mitochondrial impairment. Brain tissue samples from TBI patients and healthy controls were subjected to RNA-sequencing analysis. Mouse hippocampal HT-22 cells were treated with inflammatory cytokine and the PGC-1α activator ZLN005. Mitochondrial function, oxidative stress, and apoptosis were assessed using Seahorse respirometry, electron microscopy, flow cytometry, and molecular assays. A TBI mouse model was established to evaluate the therapeutic effects of ZLN005. Transcriptome profiling revealed downregulation of mitochondrial oxidative phosphorylation (OXPHOS) genes, particularly those encoded by the mitochondrial genome, along with enrichment of neurodegenerative pathways in TBI patients. Concomitantly, pro-inflammatory signaling pathways showed upregulation. In vitro studies demonstrated that inflammatory cytokine TNF-α treatment impaired mitochondrial respiration, induced oxidative stress and apoptosis in HT-22 cells, which could be rescued by ZLN005-mediated PGC-1α activation and restoration of OXPHOS gene expression. Administration of ZLN005 in the TBI mouse model alleviated neuronal cell death, preserved mitochondrial integrity, normalized OXPHOS gene levels in brain tissues, and improved cognitive function. This study uncovers a mechanistic link between inflammation-induced downregulation of mitochondrial OXPHOS genes and neuronal damage in TBI. Targeting this pathway by activating PGC-1α represents a potential therapeutic strategy for TBI.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798918","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}