Acta biochimica et biophysica Sinica最新文献

{"title":"SIRPα modulates the podocyte cytoskeleton through influencing the phosphorylation of FAK at tyrosine residue 597.","authors":"Yuanyuan Xia, Yue Zhao, Jing Tian, Xue Yang, Yun Fan, Shihui Dong, Fan Yang, Mingchao Zhang, Caihong Zeng","doi":"10.3724/abbs.2024198","DOIUrl":"https://doi.org/10.3724/abbs.2024198","url":null,"abstract":"<p><p>Signal regulatory protein α (SIRPα) is recognized as a significant transmembrane protein within the glomeruli that is specifically localized in podocytes, where it plays a role in modulating downstream signaling pathways through phosphorylation. Upon tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) within SIRPα, protein tyrosine phosphatases are recruited to facilitate the dephosphorylation of downstream signals. Nevertheless, the specific downstream signaling pathways affected by this mechanism have yet to be elucidated. In this study, phosphoproteomic analysis is conducted on podocytes with SIRPα deficiency to identify proteins whose phosphorylation is regulated by SIRPα and the associated signaling pathways in human podocytes. The results reveal significant alterations in biological processes related to cytoskeleton arrangement and cytoskeleton protein binding. Specifically, an increase in FAK tyrosine phosphorylation at Y576 is identified as a potentially crucial signal of the influence of SIRPα on the podocyte cytoskeleton. Our study suggests that SIRPα may facilitate podocyte cytoskeleton rearrangement and migration through the Src/FAK/p38 MAPK signaling pathway. For the first time, we discover increased level of SIRPα, which is strongly linked to urinary protein, in the urine of patients with nephrotic syndrome (NS). Additionally, an increase in urinary FAK level is observed in NS patients, which is positively correlated with both urinary protein level and urinary SIRPα level. These findings suggest that SIRPα and FAK may serve as promising biomarkers for podocytopathies.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase.","authors":"Ming-Jie Hou, Xuanqi Huang, Bao Ting Zhu","doi":"10.3724/abbs.2024165","DOIUrl":"10.3724/abbs.2024165","url":null,"abstract":"<p><p>Protein disulfide isomerase (PDI) was recently shown to be an upstream mediator of erastin-induced, glutathione depletion-associated ferroptosis through its catalysis of nitric oxide synthase (NOS) dimerization and nitric oxide (NO) accumulation. A recent study reported that RSL3, a known ferroptosis inducer and glutathione peroxidase 4 (GPX4) inhibitor, can inhibit thioredoxin reductase 1 (TrxR1). The present study seeks to test the hypothesis that RSL3 may, through its inhibition of TrxR1, facilitate PDI activation ( <i>i</i>. <i>e</i>., in a catalytically active, oxidized state), thereby enhancing RSL3-induced ferroptosis through NOS dimerization and NO accumulation. Using HT22 mouse neuronal cells as an <i>in vitro</i> model, we show that treatment of these cells with RSL3 strongly increases NOS protein levels and that PDI-mediated NOS dimerization is activated by RSL3, resulting in NO accumulation. Mechanistically, we find that PDI is activated in cells treated with RSL3 because of its inhibition of TrxR1, and the activated PDI then catalyzes NOS dimerization, which is followed by the accumulation of cellular NO, ROS and lipid-ROS and ultimately ferroptotic cell death. Genetic or pharmacological inhibition of PDI or TrxR1 partially abrogates RSL3-induced NOS activation and the subsequent accumulation of cellular NO, ROS/lipid-ROS, and ultimately ferroptosis in HT22 cells. The results of this study clearly show that PDI activation resulted from RSL3 inhibition of TrxR1 activity contributes crucially to RSL3-induced ferroptosis in a cell culture model through the PDI→NOS→NO→ROS/lipid-ROS pathway, in addition to its known inhibition of GPX4 activity.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in PIWI-piRNA function in female reproduction in mammals.","authors":"Xiaolong Lv, Hongdao Zhang, Ligang Wu","doi":"10.3724/abbs.2024195","DOIUrl":"10.3724/abbs.2024195","url":null,"abstract":"<p><p>PIWI-interacting RNAs (piRNAs), which associate with PIWI clade Argonaute proteins to form piRNA-induced silencing complexes (piRISCs) in germline cells, are responsible for maintaining genomic integrity and reproductive function through transcriptional or post-transcriptional suppression of transposable elements and regulation of protein-coding genes. Recent discoveries of crucial PIWI-piRNA functions in oogenesis and embryogenesis in golden hamsters suggest an indispensable role in female fertility that has been obscured in the predominant mouse model of PIWI-piRNA pathway regulation. In particular, studies of piRNA expression dynamics, functional redundancies, and compositional variations across mammal species have advanced our understanding of piRNA functions in male and, especially, female reproduction. These findings further support the use of hamsters as a more representative model of piRNA biology in mammals. In addition to discussing these new perspectives, the current review also covers emerging directions for piRNA research, its implications for female fertility, and our fundamental understanding of reproductive mechanisms.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mutation in SMARCB1 associated with adult Coffin-Siris syndrome and meningioma.","authors":"Zhenglong Guo, Jie Bai, Yang Liu, Xianwei Zhang, Wenke Yang, Jinming Wang, Yuwei Zhang, Hai Xiao, Bingtao Hao, Shixiu Liao","doi":"10.3724/abbs.2024204","DOIUrl":"https://doi.org/10.3724/abbs.2024204","url":null,"abstract":"<p><p><i>SMARCB1</i> encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the <i>SMARCB1</i> gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report a family of two adult CSS3 patients with a novel missense <i>SMARCB1</i> mutation (c.1091A>C, p.Lys364Thr) identified through whole-exome sequencing (WES). Both patients exhibit selective difficulties in verbal learning and experience language delays. Additionally, the development of meningioma is confirmed in one of the patients. Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the <i>SMARCB1</i> gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The peripheral Atf3 ⁺ neuronal population is responsible for nerve regeneration at the early stage of nerve injury revealed by single-cell RNA sequencing.","authors":"Li Liu, Junhui Chen, Wen Yin, Po Gao, Yinghui Fan, Daxiang Wen, Yingfu Jiao, Weifeng Yu","doi":"10.3724/abbs.2024169","DOIUrl":"https://doi.org/10.3724/abbs.2024169","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) can transform primary somatosensory neurons to a regenerative state. However, the details of the transcriptomic changes associated with the nerve regeneration of somatosensory neurons remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) is conducted on mouse dorsal root ganglion (DRG) cells after the early stage of nerve injury on day 3 after chronic constriction injury (CCI). We observe that a novel CCI-induced neuronal population (CIP) emerge and express high levels of activating transcription factor ( <i>Atf3</i>), a neuronal injury marker. CIP neurons highly express regeneration-associated genes (RAGs) and are enriched in regeneration-related gene ontology (GO) terms, suggesting that these neurons can constitute a pro-regenerative population. Moreover, intercellular communication networks show that CIP neurons closely communicate with satellite glial cells (SGCs) and specifically transmit strong <i>Fgf3</i>- <i>Fgfr1</i> signaling to SGCs, which could initiate regeneration-associated transcriptional changes in SGCs. We also confirm that regenerative progress occurs at the early stage of nerve injury because immunohistochemistry shows that the expression of ATF3 is significantly increased beginning at 3 days post-CCI and decreased at 1 month post-CCI. Our bioinformatics analysis at single-cell resolution advances the knowledge of regenerative dynamic transcriptional changes in DRG cells after injury and the underlying molecular mechanisms involved.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma.","authors":"Hao Dong, Kaixuan Sun, Xuejie Wang, Meimei Cui, Yaping Ma, Kexin Li, Wanli Duan, Hongxing Zhang, Liying Zhang, Zhimei Sheng, Maotao He, Baogang Zhang","doi":"10.3724/abbs.2024168","DOIUrl":"https://doi.org/10.3724/abbs.2024168","url":null,"abstract":"<p><p>Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis <i>in vivo</i> and <i>in vitro</i>. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMG-1 serves as a prognostic indicator for the radiotherapy response in head and neck squamous cell carcinoma xenografts and patients.","authors":"Xiaofeng Wang, Yuxia Zou, Ren-Bo Ding, Xueying Lyu, Yuanfeng Fu, Xuejun Zhou, Zhihua Sun, Jiaolin Bao","doi":"10.3724/abbs.2024180","DOIUrl":"10.3724/abbs.2024180","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA potentiates the therapeutic efficacy of glucocorticoids in lipopolysaccharide-treated HEI-OC1 cells through modulation of the FOXP3/Nrf2 signaling pathway.","authors":"Jie Li, Xiaoyan Zhu, Shiming Ye, Qi Dong, Jie Hou, Jing Liu, Wandong She","doi":"10.3724/abbs.2024194","DOIUrl":"https://doi.org/10.3724/abbs.2024194","url":null,"abstract":"<p><p>Glucocorticoids (GCs) are commonly used to treat sudden sensorineural hearing loss (SSNHL), although some patients are resistant to this therapeutic approach. Clinical studies have demonstrated the efficacy of tanshinone IIA (TA) in combination with GC for managing various human ailments. However, it remains unclear whether TA can mitigate GC resistance in SSNHL. Our aim is to elucidate the role of NRF2-induced transcriptional regulation of HDAC2 in influencing GC resistance and investigate the involvement of TA-related molecular pathways in GC resistance. Here, HEI-OC1 cells are treated with lipopolysaccharide (LPS) to establish an <i>in vitro</i> model for SSNHL. The cells are subsequently treated with dexamethasone (DXE) or DXE+TA. RT-qPCR and western blot analysis are used to measure the mRNA and protein levels of Forkhead box P3 (FOXP3), nuclear factor erythroid 2-related factor 2 (NRF2), and histone deacetylase 2 (HDAC2). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays are carried out to assess cell proliferation. Flow cytometry analysis is performed to evaluate apoptosis. Mechanistic studies involve chromatin immunoprecipitation (ChIP), luciferase reporter, and DNA pull-down assays. Our results show that treatment with TA+DEX significantly increases proliferation and suppresses apoptosis in LPS-treated HEI-treated OC1 cells. TA upregulates HDAC2 expression by activating NRF2-mediated transcription of HDAC2, with the NRF2-HDAC2 binding site located at bases 419-429 (ATGACACTCCA) in the promoter sequence of <i>HDAC2</i>. Furthermore, TA upregulates FOXP3 expression to activate NRF2 transcription, with the predicted FOXP3-binding site located at bases 864-870 (GCAAACA) in the promoter sequence of <i>NRF2</i>. In summary, these findings suggest that TA enhances the therapeutic effects of GC on the proliferation and apoptosis of HEI OC1 cells by increasing FOXP3/Nrf2 expression. These results indicate that TA may be promising for ameliorating GC resistance in patients with SSNHL.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Clitoria ternatea</i> L. flower-derived anthocyanins and flavonoids inhibit bladder cancer growth by suppressing SREBP1 pathway-mediated fatty acid synthesis.","authors":"Chenkai Liu, Jue Liu, Gao Liu, Yusong Song, Xiuyu Yang, Honglei Gao, Cheng Xiang, Jie Sang, Tianrui Xu, Jun Sang","doi":"10.3724/abbs.2024192","DOIUrl":"https://doi.org/10.3724/abbs.2024192","url":null,"abstract":"<p><p><i>Clitoria ternatea</i> L. flowers are used as traditional herbal medicines and are known for their advanced pharmacological activities. Flavonoids and anthocyanins reportedly contribute to the therapeutic properties of <i>C</i>. <i>ternatea</i> flowers; however, their potential anti-bladder cancer effects and molecular mechanisms remain unknown. In this study, flavonoid- and anthocyanin-rich samples from <i>C</i>. <i>ternatea</i> flowers (DDH) are prepared via macroporous resin-based extraction coupled with an efficient and reliable two-dimensional UPLC-DAD-MS/MS method. <i>In vitro</i> and <i>in vivo</i> studies reveal that DDH can inhibit bladder cancer cell growth and enhance the anti-bladder cancer activity of cisplatin. RNA-seq combined with KEGG analysis reveals that fatty acid synthesis is closely related to the anti-bladder cancer effect of DDH. Furthermore, DDH dose-dependently reduces cellular fatty acid levels in bladder cancer cells, and the addition of fatty acids significantly mitigates DDH-induced cell growth inhibition. Subsequent findings reveal that DDH downregulates sterol regulatory element-binding protein 1 (SREBP1), a key transcriptional regulator of <i>de novo</i> fatty acid synthesis in cancer cells, and its downstream targets (FASN, SCD1, and ACC). Additionally, this study demonstrates that gallic acid not only enhances the stability of DDH but also synergistically potentiates its anti-bladder cancer activity. Our study suggests that targeting the SREBP1 pathway is an effective strategy in bladder cancer therapy, and the ability of DDH to induce cell death by inhibiting the SREBP1 pathway and its good tolerance in mice make it a promising strategy for preventing and treating bladder cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Battling pain from osteoarthritis: causing novel cell death.","authors":"Yuheng Zhang, Huaqiang Tao, Liyuan Zhang, Xueyan Li, Yi Shi, Wen Sun, Wenlong Chen, Yuhu Zhao, Liangliang Wang, Xing Yang, Chengyong Gu","doi":"10.3724/abbs.2024189","DOIUrl":"https://doi.org/10.3724/abbs.2024189","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}