Cellular & Molecular Biology Letters最新文献

{"title":"Salivary gland protective and antiinflammatory effects of genistein in Sjögren's syndrome by inhibiting Xist/ACSL4-mediated ferroptosis following binding to estrogen receptor-alpha.","authors":"Tianjiao Mao, Wei Wei, Bo Chen, Yixin Chen, Shuqi Liang, Guiping Chen, Zhuoyuan Liu, Xiaodan Wu, Lihong Wu, Xiaomeng Li, Nobumoto Watanabe, Kevin H Mayo, Janak L Pathak, Jiang Li","doi":"10.1186/s11658-024-00667-6","DOIUrl":"10.1186/s11658-024-00667-6","url":null,"abstract":"<p><strong>Background: </strong>Sjögren's syndrome (SS) is an autoimmune disease with limited effective treatment options. This study aimed to explore the underlying mechanism by which genistein-estrogen receptor alpha (ERα) complex targets X-inactive specific transcript (Xist) then leads to the inhibition of ferroptosis by regulating acyl-CoA synthetase long-chain family member 4 (ACSL4) expression in salivary gland epithelial cells (SGECs) to attenuate SS.</p><p><strong>Methods: </strong>The effects of genistein treatment on the progression and underlying mechanism of SS were investigated using nondiabetic obese (NOD)/LtJ mice in vivo and Interferon-γ (IFNγ)-treated SGECs in vitro. Water intake and saliva flow rate were measured to evaluate the severity of xerostomia. Hematoxylin-eosin staining, real-time quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay were conducted to examine the pathological lesions. Western blotting and immunohistochemistry analysis were used to evaluate the protein expression. RNA sequencing and RNA fluorescence in situ hybridization were employed to verify the relationship between Xist and ACSL4. Surface plasmon resonance, molecular docking, and molecular dynamics were used to investigate the binding between genistein and ERα. Furthermore, a chromatin immunoprecipitation assay was used to analyze ERα-XIST promoter interactions. The levels of malondialdehyde, glutathione, Fe²⁺, and mitochondrial changes were measured to evaluate ferroptosis of SGECs.</p><p><strong>Results: </strong>In NOD/LtJ mice, a ferroptosis phenotype was observed in salivary glands, characterized by downregulated Xist and upregulated X chromosome inactivation gene Acsl4. Genistein significantly alleviated SS symptoms, upregulated the Xist gene, and downregulated Acsl4 expression. Genistein upregulated Xist expression in the salivary gland of NOD/LtJ mice via the ERα signaling pathway. It downregulated Acsl4 and ferroptosis in the salivary glands of NOD/LtJ mice. IFNγ-treatment induced inflammation and ferroptosis in SGECs. Genistein binding to ERα upregulated XIST, and aquaporin 5 expression, downregulated ACSL4, and SS antigen B expression, and reversed ferroptosis in SGECs. Genistein mitigated inflammation and ferroptosis in SGECs by upregulated-XIST-mediated ACSL4 gene silencing.</p><p><strong>Conclusions: </strong>Genistein binding to ERα targets Xist, leading to inhibiting ferroptosis by regulating ACSL4 expression in SGECs. This finding provides evidence for genistein as a treatment for SS and identifies Xist as a novel drug target for SS drug development, offering great promise for improving SS outcomes.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"147"},"PeriodicalIF":9.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SENP3 mediates deSUMOylation of SIX1 to promote prostate cancer proliferation and migration.","authors":"Zhenlong Shao, Shutong Liu, Wenshuang Sun, Xuefen Zhuang, Shusha Yin, Ji Cheng, Xiaohong Xia, Yuning Liao, Jinbao Liu, Hongbiao Huang","doi":"10.1186/s11658-024-00665-8","DOIUrl":"10.1186/s11658-024-00665-8","url":null,"abstract":"<p><strong>Background: </strong>Sentrin/SUMO-specific protease 3 (SENP3) is essential to regulate protein stability and function in normal and cancer cells. Nevertheless, its role and action mechanisms in prostate cancer (PCa) remain elusive. Thus, clarification of SENP3's involvement and the SUMOylation process in PCa is pivotal for discovering potential targets and understanding SUMOylation dynamics.</p><p><strong>Methods: </strong>Cell viability, EdU staining, live cell imaging, and cell cycle assays were used to determine proliferation of PCa cells. Transwell and wound-healing assays were used to detect migration of PCa cells. The interaction between SENP3 and SIX1 was determined by co-immunoprecipitation, western blotting, and immunofluorescence assays. Xenograft models established on NOD-SCID mice were used to evaluate in vivo effects post SENP3 knockdown. Immunohistochemistry was performed to investigate the expression of SENP3 in PCa tissues.</p><p><strong>Results: </strong>This study found that SENP3 is highly expressed in PCa cell lines and tissues from PCa patients. Overexpressed SENP3 is associated with metastatic malignancy in PCa. Various in vivo and in vitro experiments confirmed that SENP3 promotes the proliferation and migration of PCa. In addition, SENP3 interacts with the SD domain of SIX1 and mediates its deSUMOylation and protein stability. Lys154 (K154) is required for the SUMOylation of SIX1. More importantly, SENP3 promotes the malignancy of PCa through the regulation of SIX1.</p><p><strong>Conclusions: </strong>We unravel the significant role of SENP3 in regulating protein stability of SIX1 and progression of PCa, which may deepen our understanding of the SUMOylation modification and provide a promising target for management of metastatic PCa.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"146"},"PeriodicalIF":9.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells.","authors":"Zeying Zhang, Di Yang, Xiaoyuan Yan, Qiujing Qiu, Jiajie Guo, Lihong Qiu","doi":"10.1186/s11658-024-00664-9","DOIUrl":"10.1186/s11658-024-00664-9","url":null,"abstract":"<p><strong>Background: </strong>Differentiating dental pulp stem cells (DPSCs) into odontoblasts is a critical process for tooth self-repair and dentine‒pulp engineering strategies in the clinic. However, the mechanism underlying the regulation of DPSC odontoblastic differentiation remains largely unknown. Here, we demonstrated that BCL-2 interacting protein 3 (BNIP3)-dependent mitophagy is associated with importin subunit beta-1 (KPNB1)-activating transcription factor 4 (ATF4), which promotes DPSC odontoblastic differentiation.</p><p><strong>Methods: </strong>The key genes involved in DPSC odontogenic differentiation were identified via bioinformatics. Stable silencing or overexpression of BNIP3 was performed to investigate its impact on DPSC differentiation in vitro (n ≥ 3). To explore the role of BNIP3 in vivo, tooth root fragments loaded with the hydrogel-transfected DPSC complex were implanted into nude mice (n ≥ 6). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) polymerase chain reaction (PCR) were conducted to explore the binding site of ATF4 to the BNIP3 promoter (n ≥ 3). Mitochondrial function experiments were performed to investigate the impact of ATF4-BNIP3 on mitochondria (n ≥ 3). Immunoprecipitation (IP) mass spectrometry (MS) was used to investigate the interaction between ATF4 and its binding protein, KPNB1. Plasmids containing wild-type (WT)/mutant (MUT)-nuclear localization signal (NLS) forms of ATF4 were constructed to determine the specific amino acid residues recognized by KPNB1 and their effects on DPSC odontoblastic differentiation (n ≥ 3).</p><p><strong>Results: </strong>Compared with those in the control group, the levels of autophagy and mitophagy, especially BNIP3-dependent mitophagy, were greater in the DPSC odontoblastic differentiation group (P < 0.05). Genetic silencing or overexpression of BNIP3 demonstrated that BNIP3 expression was positively correlated with the transition of DPSCs into odontoblasts both in vitro and in vivo (P < 0.05). ATF4 regulates the expression of BNIP3 by directly binding to approximately -1292 to -1279 bp and approximately -1185 to -1172 bp within the BNIP3 promoter region, which is associated with mitophagy and mitochondrial reactive oxygen species (mtROS) levels (P < 0.05). Moreover, ATF4 increased mitophagy, mitochondrial function, and cell differentiation potential via BNIP3 (P < 0.05). Mechanistically, KPNB1 is a novel interacting protein of ATF4 that specifically recognizes amino acids (aa) 280-299 within ATF4 to control its translocation into the nucleus and subsequent transcription and differentiation processes (P < 0.05).</p><p><strong>Conclusions: </strong>We reported that the critical role of KPNB1/ATF4/BNIP3 axis-dependent mitophagy could provide new cues for the regeneration of the dental pulp‒dentin complex in DPSCs.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"145"},"PeriodicalIF":9.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-1269a/PCDHGA9/CXCR4/β-catenin pathway promotes colorectal cancer invasion and metastasis.","authors":"Haitao Mei, Qingshan Luo, Junyong Weng, Jialing Hao, Jinfeng Cai, Runkai Zhou, Ce Bian, Yingzi Ye, Shengzheng Luo, Yugang Wen","doi":"10.1186/s11658-024-00656-9","DOIUrl":"10.1186/s11658-024-00656-9","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This research focuses on investigating the impact and underlying molecular mechanisms of protocadherin gamma subfamily A, 9 (PCDHGA9) on the invasion and metastasis of CRC, aiming to identify more precise molecular markers for the diagnosis and prognosis of CRC.</p><p><strong>Methods: </strong>PCDHGA9 expression was detected using quantitative real-time quantitative polymerase chain reaction (RT-qPCR) in 63 pairs of colorectal cancer tissues. Differential gene expression from high-throughput sequencing was analyzed using ingenuity pathway analysis (IPA) to explore the biological functions of PCDHGA9 and its potential regulated genes. Bioinformatics tools were employed to explore potential upstream regulatory microRNAs of PCDHGA9. Dual-luciferase assays were performed to demonstrate the regulation between PCDHGA9 and miR-1269a. Protein mass spectrometry suggested an interaction between PCDHGA9 and HOXA1. JASPAR predicted that HOXA1 may act as a transcription factor of CXCR4. Coimmunoprecipitation, dual-luciferase assays, and nuclear-cytoplasmic fractionation experiments confirmed the molecular mechanism involving PCDHGA9, CXCR4, HOXA1, and β-catenin. Transwell, wound healing, and western blot assays were conducted to confirm the impact of PCDHGA9, miR-1269a, and CXCR4 on the invasion, metastasis, and epithelial-mesenchymal transition (EMT) functions of CRC cells in in vitro experiments. A whole-body fluorescence imaging system was used to evaluate the combined impact of miR-1269a and PCDHGA9 on the invasion and metastasis of CRC in in vivo experiments.</p><p><strong>Results: </strong>The expression of PCDHGA9 was found to be lower in CRC tissues compared with their corresponding adjacent tissues. Low expression of PCDHGA9 potentially correlated with worse prognosis and increased chances of invasion and metastasis in CRC. miR-1269a was highly expressed in CRC tissues and acted as a negative regulator for PCDHGA9, promoting invasion, migration, and EMT of CRC cells. PCDHGA9's interaction with HOXA1 downregulated CXCR4, a transcription factor, leading to accumulation of β-catenin and further promoting invasion, migration, and EMT of CRC cells.</p><p><strong>Conclusions: </strong>PCDHGA9, acting as a tumor suppressor, is downregulated by miR-1269a. The low level of PCDHGA9 activates the Wnt/β-catenin pathway by releasing its interaction with HOXA1, promoting the expression of CXCR4, and causing invasion, migration, and EMT in CRC.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"144"},"PeriodicalIF":9.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells.","authors":"Alp Yigit Özdemir, Kateřina Hofbauerová, Vladimír Kopecký, Jiří Novotný, Vladimír Rudajev","doi":"10.1186/s11658-024-00657-8","DOIUrl":"10.1186/s11658-024-00657-8","url":null,"abstract":"<p><p>Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer's disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH₄OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH₄OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH₄OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"143"},"PeriodicalIF":9.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.","authors":"Hongkun Hu, Jinxin Tang, Hua Wang, Xiaoning Guo, Chao Tu, Zhihong Li","doi":"10.1186/s11658-024-00662-x","DOIUrl":"10.1186/s11658-024-00662-x","url":null,"abstract":"<p><p>RNA splicing is a fundamental step of gene expression. While constitutive splicing removes introns and joins exons unbiasedly, alternative splicing (AS) selectively determines the assembly of exons and introns to generate RNA variants corresponding to the same transcript. The biogenesis of circular RNAs (circRNAs) is inextricably associated with AS. Back-splicing, the biogenic process of circRNA, is a special form of AS. In cancer, both AS and circRNA deviate from the original track. In the present review, we delve into the intricate interplay between AS and circRNAs in the context of cancer. The relationship between AS and circRNAs is intricate, where AS modulates the biogenesis of circRNAs and circRNAs in return regulate AS events. Beyond that, epigenetic and posttranscriptional modifications concurrently regulate AS and circRNAs. On the basis of this modality, we summarize current knowledge on how splicing factors and other RNA binding proteins regulate circRNA biogenesis, and how circRNAs interact with splicing factors to influence AS events. Specifically, the feedback loop regulation between circRNAs and AS events contributes greatly to oncogenesis and cancer progression. In summary, resolving the crosstalk between AS and circRNA will not only provide better insight into cancer biology but also provoke novel strategies to combat cancer.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"142"},"PeriodicalIF":9.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.","authors":"Zhanhuan Su, Yang Zhang, Jingqiong Tang, Yanhong Zhou, Chen Long","doi":"10.1186/s11658-024-00661-y","DOIUrl":"10.1186/s11658-024-00661-y","url":null,"abstract":"<p><p>HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1's involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"141"},"PeriodicalIF":9.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m⁶A-modified circCacna1c regulates necroptosis and ischemic myocardial injury by inhibiting Hnrnpf entry into the nucleus.","authors":"Yi Jia, Xiaosu Yuan, Luxin Feng, Qingling Xu, Xinyu Fang, Dandan Xiao, Qi Li, Yu Wang, Lin Ye, Peiyan Wang, Xiang Ao, Jianxun Wang","doi":"10.1186/s11658-024-00649-8","DOIUrl":"10.1186/s11658-024-00649-8","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) are differentially expressed in various cardiovascular diseases, including myocardial infarction (MI) injury. However, their functional role in necroptosis-induced loss of cardiomyocytes remains unclear. We identified a cardiac necroptosis-associated circRNA transcribed from the Cacna1c gene (circCacna1c) to investigate the involvement of circRNAs in cardiomyocyte necroptosis.</p><p><strong>Methods: </strong>To investigate the role of circCacna1c during oxidative stress, H9c2 cells and neonatal rat cardiomyocytes were treated with hydrogen peroxide (H₂O₂) to induce reactive oxygen species (ROS)-induced cardiomyocyte death. The N⁶-methyladenosine (m⁶A) modification level of circCacna1c was determined by methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP-qPCR) analysis. Additionally, an RNA pull-down assay was performed to identify interacting proteins of circCacna1c in cardiomyocytes, and the regulatory role of circCacna1c in target protein expression was tested using a western blotting assay. Furthermore, the MI mouse model was constructed to analyze the effect of circCacna1c on heart function and cardiomyocyte necroptosis.</p><p><strong>Results: </strong>The expression of circCacna1c was found to be reduced in cardiomyocytes exposed to oxidative stress and in mouse hearts injured by MI. Overexpression of circCacna1c inhibited necroptosis of cardiomyocytes induced by hydrogen peroxide and MI injury, resulting in a significant reduction in myocardial infarction size and improved cardiac function. Mechanistically, circCacna1c directly interacts with heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in the cytoplasm, preventing its nuclear translocation and leading to reduced Hnrnpf levels within the nucleus. This subsequently suppresses Hnrnpf-dependent receptor-interacting protein kinase 1 (RIPK1) expression. Furthermore, fat mass and obesity-associated protein (FTO) mediates demethylation of m⁶A modification on circCacna1c during necrosis and facilitates degradation of circCacna1c.</p><p><strong>Conclusion: </strong>Our study demonstrates that circCacna1c can improve cardiac function following MI-induced heart injury by inhibiting the Hnrnpf/RIPK1-mediated cardiomyocyte necroptosis. Therefore, the FTO/circCacna1c/Hnrnpf/RIPK1 axis holds great potential as an effective target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"140"},"PeriodicalIF":9.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation.","authors":"Izabela Czyzynska-Cichon, Jerzy Kotlinowski, Oliwia Blacharczyk, Magdalena Giergiel, Konrad Szymanowski, Sara Metwally, Kamila Wojnar-Lason, Ewelina Dobosz, Joanna Koziel, Malgorzata Lekka, Stefan Chlopicki, Bartlomiej Zapotoczny","doi":"10.1186/s11658-024-00655-w","DOIUrl":"10.1186/s11658-024-00655-w","url":null,"abstract":"<p><strong>Background: </strong>Liver sinusoidal endothelial cells (LSECs) have transcellular pores, called fenestrations, participating in the bidirectional transport between the vascular system and liver parenchyma. Fenestrated LSECs indicate a healthy phenotype of liver while loss of fenestrations (defenestration) in LSECs is associated with liver pathologies.</p><p><strong>Methods: </strong>We introduce a unique model of systemic inflammation triggered by the deletion of Mcpip1 in myeloid leukocytes (Mcpip1^fl/flLysM^Cre) characterised by progressive alterations in LSEC phenotype. We implement multiparametric characterisation of LSECs by using novel real-time atomic force microscopy supported with scanning electron microscopy and quantitative fluorescence microscopy. In addition, we provide genetic profiling, searching for characteristic genes encoding proteins that might be connected with the structure of fenestrations.</p><p><strong>Results: </strong>We demonstrate that LSECs in Mcpip1^fl/flLysM^Cre display two phases of defenestration: the early phase, with modest defenestration that was fully reversible using cytochalasin B and the late phase, with severe defenestration that is mostly irreversible. By thorough analysis of LSEC porosity, elastic modulus and actin abundance in Mcpip1^fl/flLysM^Cre and in response to cytochalasin B, we demonstrate that proteins other than actin must be additionally responsible for inducing open fenestrations. We highlight several genes that were severely affected in the late but not in the early phase of LSEC defenestration shedding a light on complex structure of individual fenestrations.</p><p><strong>Conclusions: </strong>The presented model of LSEC derived from Mcpip1^fl/flLysM^Cre provides a valuable reference for developing novel strategies for LSEC refenestration in the early and late phases of liver pathology.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"139"},"PeriodicalIF":9.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death.","authors":"Jiufeng Xie, Cui Yuan, Sen Yang, Zhenling Ma, Wenqing Li, Lin Mao, Pengtao Jiao, Wei Liu","doi":"10.1186/s11658-024-00659-6","DOIUrl":"10.1186/s11658-024-00659-6","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"29 1","pages":"138"},"PeriodicalIF":9.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}