{"title":"The potential role of AhR/NR4A1 in androgen-dependent prostate cancer: Focus on TCDD-induced ferroptosis.","authors":"Xiang Chen, Yuan Yao, Guotong Gong, Tianji He, Chenjun Ma, Jingsong Yu","doi":"10.1139/bcb-2024-0155","DOIUrl":"https://doi.org/10.1139/bcb-2024-0155","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genwang Wang, Di Liu, Junzhi Leng, Dong Jin, Qi Wang, Hao Wang, Yang Bu, Feng Wang, Yongfeng Hui
{"title":"TMCO1 regulates energy metabolism and mitochondrial function of hepatocellular carcinoma cells through TOMM20, affecting the growth of subcutaneous graft tumors and infiltration of CAFs.","authors":"Genwang Wang, Di Liu, Junzhi Leng, Dong Jin, Qi Wang, Hao Wang, Yang Bu, Feng Wang, Yongfeng Hui","doi":"10.1139/bcb-2024-0091","DOIUrl":"10.1139/bcb-2024-0091","url":null,"abstract":"<p><p>This study mainly shows the role of endoplasmic reticulum transmembrane and coiled coil domains 1 (TMCO1) in the regulatory mechanism of hepatocellular carcinoma (HCC). Invasion and migration capacity were detected by Transwell and wound healing after TMCO1 and TOMM20 overexpression and knockdown, and mitochondrial function was detected through reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (MMP), and ATP production. A model of subcutaneous tumor formation in nude mice was established to detect the effect of TMCO1 on tumor formation. The results showed that overexpression of TMCO1 significantly promoted HCC cell metastasis, promoted cell proliferation and ATP production, inhibited cell apoptosis, mPTP opening and ROS production, mediated the increase of MMP level and cytoskeletal remodeling. However, knocking down TMCO1 can have the opposite effect. More importantly, knocking down TOMM20 can block the regulation effect of TMCO1, and TOMM20 overexpression can alleviate the inhibitory effect of knocking down TMCO1 on the development of liver cancer cells. In animal models, knockdown of TMCO1 expression significantly inhibited the growth of subcutaneous implant tumors. This suggests that TMCO1 may be a potential and valuable therapeutic target for liver cancer.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Perturbation of calcium homeostasis invokes eryptosis-like cell death in enucleated bone marrow stem cells.","authors":"Wei Yan, Ruolan Wu, Yingying Lee, Liqun Xu, Xiao Li, Junwei Li, Ronghao Deng, Xing Fan, Yilang Wu, Haibao Zhu, Aihua Mao, Jianxin Shen, Chi-Ju Wei","doi":"10.1139/bcb-2024-0106","DOIUrl":"https://doi.org/10.1139/bcb-2024-0106","url":null,"abstract":"<p><p>Enucleated cells, also known as cytoplasts, are valuable tools with a wide range of applications. However, their potential for bio-engineering is greatly restricted by the short lifespan. We postulated that the enucleation process damages the integrity of the plasma membrane and thus activates a cell death program(s). The results showed that a tiny hole was generated transiently on the plasma membrane when the nucleus was spun off, while force-gated ion channels were activated in response to the pulling by the nucleus. Influx of extracellular calcium stimulated the opening of calcium channels and the release of calcium from endoplasmic reticulum and mitochondria. Long lasting calcium transient increased protein phosphorylation and activated caspase 9 and calpain proteinase activities. Subsequently, mitochondria membrane permeability and Reactive Oxygen Species (ROS) levels were significantly elevated, which eventually led to eryptosis-like cell death. When extracellular calcium was maintained at optimal concentration, the lifespan of enucleated cells was extended; however, huge amounts of vacuoles appeared in the cytoplasm, possibly derived from enlarged autophagosomes. Inhibition of vacuolation by inhibitors of autophagy or in co-culture with primary muscle cells did not rescue cells dying from the paraptosis-like pathway. These results offer valuable insights for further investigation into the intricate mechanisms underlying enucleated cell death.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoying Li, Shenggui Liu, Siqi Wang, Xinghui Ai, Lin Wei
{"title":"1-Deoxynojirimycin affects high glucose-induced pancreatic beta-cell dysfunction through regulating CEBPA expression and AMPK pathway.","authors":"Xiaoying Li, Shenggui Liu, Siqi Wang, Xinghui Ai, Lin Wei","doi":"10.1139/bcb-2024-0128","DOIUrl":"10.1139/bcb-2024-0128","url":null,"abstract":"<p><p>This study aims to explore the role of 1-deoxynojirimycin (DNJ) in high glucose-induced β-cells and to further explore the molecular mechanism of DNJ effect on β-cells through network pharmacology. In the study, high glucose treatment of mouse INS-1 cells inhibited cell proliferation and insulin secretion, decreased the expression of Bcl-2 protein and Ins1 and Ins2 genes, promoted apoptosis, and increased cleaved caspase-3 and cleaved caspase-9 expression levels as well as intracellular reactive oxygen species production. DNJ treatment significantly restored the dysfunction of INS-1 cells induced by high glucose, and DNJ showed no toxicity to normal INS-1 cells. Silencing CEBPA promoted, while overexpression of CEBPA relieved the dysfunction of pancreatic β-cells induced by high glucose. DNJ treatment partially restored the pancreatic β-cell dysfunction caused by silencing CEBPA. In conclusion, DNJ can inhibit high glucose-induced pancreatic β-cell dysfunction by promoting the expression of CEBPA.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengmeng Liu, Yingrui Li, Xin Yuan, Shunkang Rong, Jianlin Du
{"title":"Novel insights into RNA polymerase II transcription regulation: transcription factors, phase separation, and their roles in cardiovascular diseases.","authors":"Mengmeng Liu, Yingrui Li, Xin Yuan, Shunkang Rong, Jianlin Du","doi":"10.1139/bcb-2024-0094","DOIUrl":"https://doi.org/10.1139/bcb-2024-0094","url":null,"abstract":"<p><p>Transcription factors (TFs) are specialized proteins that bind DNA in a sequence-specific manner and modulate RNA polymerase II (Pol II) in multiple steps of the transcription process. Phase separation is a spontaneous or driven process that can form membrane-less organelles called condensates. By creating different liquid phases at active transcription sites, the formation of transcription condensates can reduce the water content of the condensate and lower the dielectric constant in biological systems, which in turn alters the structure and function of proteins and nucleic acids in the condensate. In RNA Pol II transcription, phase separation formation shortens the time at which TFs bind to target DNA sites and promotes transcriptional bursting. RNA Pol II transcription is engaged in developing several diseases, such as cardiovascular disease, by regulating different TFs and mediating the occurrence of phase separation. This review aims to summarize the advances in the molecular mechanisms of RNA Pol II transcriptional regulation, in particular the effect of TFs and phase separation. The role of RNA Pol II transcriptional regulation in cardiovascular disease will be elucidated, providing potential therapeutic targets for the management and treatment of cardiovascular disease.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of the polybromo-associated BAF complex in development.","authors":"JinYoung Park, Jacob G Kirkland","doi":"10.1139/bcb-2024-0224","DOIUrl":"10.1139/bcb-2024-0224","url":null,"abstract":"<p><p>Chromatin is dynamically regulated during development, where structural changes affect the transcription of genes required to promote different cell types. One of the chromatin regulatory factors responsible for transcriptional regulation during development is the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, an ATP-dependent chromatin remodeling factor conserved throughout eukaryotes. The catalytic subunit of this complex, BRG1, is shared in all three SWI/SNF complexes subfamilies and is essential for developing most cell lineages. Interestingly, many human developmental diseases have correlative or causative mutations in different SWI/SNF subunits. Many polybromo-associated BAF (pBAF) complex-specific subunit genetic alterations result in developmental failures in tissue-specific ways. This observation suggests that the pBAF complex plays a vital role in development and differentiation, and studying the pBAF complex may provide an opportunity to better understand gene regulation during development. In this mini-view, we will focus on the functions of pBAF-specific subunits and their influence on the development of various cell and tissue types by regulating developmental gene expression.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gallein, G protein βγ subunits inhibitor, suppresses the TGF-α-induced migration of hepatocellular carcinoma cells via inhibition of the c-Jun N-terminal kinase.","authors":"Rie Matsushima-Nishiwaki, Yoh Honda, Haruhiko Tokuda, Osamu Kozawa","doi":"10.1139/bcb-2024-0141","DOIUrl":"https://doi.org/10.1139/bcb-2024-0141","url":null,"abstract":"<p><p>G protein-coupled receptor (GPCR) signaling regulates a wide range of pathophysiological cell functions via G protein α and βγ subunits. Small molecules targeting the subunits of Gα and Gβγ have been developed as cancer therapeutics. We have previously reported that transforming growth factor-α (TGF-α) induces the migration of human hepatocellular carcinoma (HCC) HuH7 cells through the activation of AKT, p38 mitogen-activated protein kinase (MAPK), Rho-kinase and c-Jun N-terminal kinase (JNK). This study aims to determine whether Gβγ subunits regulate the TGF-α-induced migration of HCC HuH7 cells using gallein, a Gβγ subunits inhibitor. The Janus family of tyrosine kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also involved in the regulation of the migration. Gallein significantly reduced the TGF-α-induced cell migration. In contrast, fluorescein, a gallein-related compound that has no effect on Gβγ subunits, failed to affect the cell migration. Gallein suppressed the TGF-α-stimulated phosphorylation of JNK without affecting the phosphorylation of epidermal growth factor receptor, AKT, p38 MAPK, target protein of Rho-kinase and STAT3. Conversely, fluorescein did not attenuate the phosphorylation of JNK. These results strongly suggest that Gβγ subunits act as positive regulators in TGF-α-induced migration of HCC cells via the JNK signalling pathway.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaqin Fang, Fenglin Song, Chunyan Gao, Zhiming Wang
{"title":"Hydrocortisone improves post-resuscitation myocardial dysfunction by inhibiting the NF-κB pathway.","authors":"Yaqin Fang, Fenglin Song, Chunyan Gao, Zhiming Wang","doi":"10.1139/bcb-2024-0162","DOIUrl":"10.1139/bcb-2024-0162","url":null,"abstract":"<p><p>Myocardial dysfunction is a major cause of early mortality after successful cardiopulmonary resuscitation (CPR) following cardiac arrest (CA). Following the return of spontaneous circulation, myocardial ischemia-reperfusion injury can activate the NF-κB pathway, leading to the transcription of inflammatory genes that impair myocardial function. While clinical studies show hydrocortisone (HC) improves outcomes in CA patients during CPR, its specific role in modulating the NF-κB pathway is unclear. In this study, we established an in vitro model by inducing hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes using Na<sub>2</sub>S<sub>2</sub>O<sub>4</sub>, followed by HC treatment. The results showed that HC treatment of H/R-injured cardiomyocytes promoted proliferation, inhibited apoptosis, and suppressed the NF-κB pathway, thereby reducing interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, inhibition of the NF-κB pathway enhanced the proliferative capacity of H/R cardiomyocytes, decreased apoptosis rates, and reduced IL-6, IL-8, and TNF-α expression levels, with these effects being further amplified by HC treatment. These findings were further supported by in vivo experiments. In conclusion, our study suggests that HC may promote H/R cardiomyocyte proliferation, inhibit apoptosis, and alleviate inflammatory responses by suppressing the NF-κB pathway, providing new evidence to support its potential clinical application in CA management.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie-Frédérique Gauthier, Giada Ostinelli, Mélissa Pelletier, Andre Tchernof
{"title":"Origin of dedifferentiated adipocyte-derived cells (DFAT) during ceiling culture in an Adiponectin Cre-Recombinase mouse model.","authors":"Marie-Frédérique Gauthier, Giada Ostinelli, Mélissa Pelletier, Andre Tchernof","doi":"10.1139/bcb-2024-0140","DOIUrl":"https://doi.org/10.1139/bcb-2024-0140","url":null,"abstract":"<p><p>Dedifferentiated adipose tissue-derived (DFAT) cells represent an attractive source of stem cells for tissue engineering and the potential treatment of several clinical conditions. Our objective was to determine whether DFAT cells originate from mature adipocytes and address whether contamination from the stromal vascular fraction (SVF) could be as a source for these cells. A murine adiponectin-creERT; mT/mG model was used with the excision of the cassette induced by tamoxifen injection for the cells expressing adiponectin (adipoq). This model allows distinguishing mature adipocytes (green fluorescence) from other SVF cell types (red fluorescence) based on the fluorescent protein expressed. Mature adipocytes and SVF cells were isolated from adipose tissues by collagenase digestion. Ceiling cultures were imaged by time-lapse microscopy. Confocal microscopy was used to follow cells over 21 days. Time-lapse microscopy experiments showed liposecretion occurring in mature adipocytes displaying green fluorescence. Confocal imaging allowed the identification of a heterogeneous cell population expressing green but also red fluorescence after 21 days of culture. Asymmetrical division of mature adipocytes was not observed. In conclusion, liposecretion of mature adipocytes is a phenomenon that can be observed in vitro and DFAT cells do originate from mature adipocytes. However, the population of DFAT cells is heterogenous.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanya Sharma, Robert Y Jomphe, Dongling Zhang, Ana C Magalhaes, Michele C Loewen
{"title":"<i>Fusarium graminearum</i> Ste2 and Ste3 receptors undergo peroxidase-induced heterodimerization when expressed heterologously in <i>Saccharomyces cerevisiae</i>.","authors":"Tanya Sharma, Robert Y Jomphe, Dongling Zhang, Ana C Magalhaes, Michele C Loewen","doi":"10.1139/bcb-2024-0104","DOIUrl":"10.1139/bcb-2024-0104","url":null,"abstract":"<p><p><i>Fusarium graminearum Fg</i>Ste2 and <i>Fg</i>Ste3 are G-protein-coupled receptors (GPCRs) shown to play roles in hyphal chemotropism and fungal plant pathogenesis in response to activity arising from host-secreted peroxidases. Here, we follow up on the observation that chemotropism is dependent on both <i>Fg</i>Ste2 and <i>Fg</i>Ste3 being present; testing the possibility that this might be due to formation of an <i>Fg</i>Ste2-<i>Fg</i>Ste3 heterodimer. Bioluminescence resonance energy transfer (BRET) analyses were conducted in <i>Saccharomyces cerevisiae</i>, where the addition of horse radish peroxidase (HRP) was found to increase the transfer of energy from the inducibly expressed <i>Fg</i>Ste3-Nano luciferase donor, to the constitutively expressed <i>Fg</i>Ste2-yellow fluorescent protein (YFP) acceptor, compared to controls. A partial response was also detected when an HRP-derived ligand-containing extract was enriched from <i>F. graminearum</i> spores and applied instead of HRP. In contrast, substitution with pheromones or an unrelated bovine GPCR, rhodopsin-YFP used as acceptor, eliminated all BRET responses. Interaction results were validated by affinity pulldown and receptor expression was validated by confocal immunofluorescence microscopy. Taken together these findings demonstrate the formation of HRP and HRP-derived ligand stimulated heterodimers between <i>Fg</i>Ste2 and <i>Fg</i>Ste3. Outcomes are discussed from the context of the roles of ligands and reactive oxygen species in GPCR dimerization.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}