BMB Reports最新文献_第2页

SLC39 and SLC30 zinc transporters: functions and potential mechanisms in cancer. SLC39和SLC30锌转运体：在癌症中的功能和潜在机制

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-05

Sung Eun Kim

引用次数: 0

Sestrin2 protects ovarian granulosa cells by regulating oxidative stress and p53-mediated apoptosis. Sestrin2通过调节氧化应激和p53介导的细胞凋亡来保护卵巢颗粒细胞。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-05

Jeongyun Bae, Joon H Lee, Jong-Seok Kim, Hwan-Woo Park, Jongdae Shin

{"title":"Sestrin2 protects ovarian granulosa cells by regulating oxidative stress and p53-mediated apoptosis.","authors":"Jeongyun Bae, Joon H Lee, Jong-Seok Kim, Hwan-Woo Park, Jongdae Shin","doi":"","DOIUrl":"","url":null,"abstract":"Reactive Oxygen Species (ROS) accumulation disrupts cellular homeostasis, leading to lipid peroxidation, mitochondrial dysfunction, DNA damage, and apoptosis. Sestrin2 (Sesn2) is a critical antioxidant protein that regulates intracellular oxidative stress and protects cells from oxidative damage and apoptosis. However, the role of Sesn2 in ovarian reproductive function remains unclear. In this study, we examined Sesn2 expression in response to oxidative stress using granulosa-like KGN cells derived from human ovarian granulosa cell tumors, mouse granulosa cells, and an oxidative stress mouse model. Additionally, we investigated the protective Sesn2 functions and its mechanisms of action in promoting granulosa cell survival. The results showed that Sesn2 expression markedly increased in granulosa cells exposed to hydrogen peroxide (H2O2) and in oxidative stress models induced by 3-nitropropionic acid (3-NP). Oxidative stress in ovarian granulosa cells increases ROS levels, decreases cell viability, and triggers apoptosis. Sesn2 silencing further aggravates granulosa cell damage, whereas targeting Sesn2 under oxidative stress conditions reduces ROS levels and modulates apoptosis through the p53/Caspase-3 signaling pathway. These findings highlight the pivotal role of Sesn2 in protecting cells against ROS-induced damage, preserving follicular health, and supporting ovarian function and reproductive capacity.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353747","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}

引用次数: 0

Improved efficiency of protein aggregate removal using ubiquitin with a signal peptide. 利用泛素和信号肽提高蛋白质集合体去除效率。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-01

Taek-Yeong Kim, Kwon-Yul Ryu

{"title":"Improved efficiency of protein aggregate removal using ubiquitin with a signal peptide.","authors":"Taek-Yeong Kim, Kwon-Yul Ryu","doi":"","DOIUrl":"","url":null,"abstract":"Lipocalin-2 (LCN2) is a protein secreted by activated astrocytes, and its signal peptide (SP) is essential for secretion and recruitment to the autophagic pathway. SP is a short sequence present at the N-terminus of secreted proteins, such as LCN2, which facilitates transport to the endoplasmic reticulum (ER). Although SP is cleaved during the initial stages of translation in the ER, it influences the subsequent pathways of mature proteins produced in the ER lumen. ER-generated proteins are secreted or recruited to the autophagic pathway. To explore this further, we sought to determine the functional role of SP from a novel perspective. In this study, we fused LCN2 SP to the N-terminus of ubiquitin (Ub), an intracellular protein used for the proteasomal degradation of misfolded proteins and autophagic degradation of protein aggregates. We demonstrated that SP enabled the secretion of free Ub and facilitated the targeting of Ub conjugates to the autophagic pathway. We also found that SP affected intracellular Ub conjugate levels by regulating their degradation via the autophagic pathway. Furthermore, the ER-generated Ub (UbE) showed increased participation in polyubiquitinating protein aggregates generated under proteotoxic stress conditions, promoting the formation of perinuclear aggresome-like structures, and recruitment to the autophagosome. It is highly likely that UbE shares a common route with protein aggregates before being recruited to autophagosomes. Thus, this study suggests that UbE confers an altered trafficking pathway compared with endogenous Ub, thereby facilitating protein aggregate clearance without altering Ub's intrinsic biochemical activity. [BMB Reports 2026; 59(3): 187-192].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"187-192"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial quantity-quality imbalance in cellular senescence: practical readouts and minimal assay bundles. 线粒体数量质量不平衡在细胞衰老：实际读数和最小的分析束。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-01

Myeongwoo Jung, Seongho Cha, Eun Kyung Lee

{"title":"Mitochondrial quantity-quality imbalance in cellular senescence: practical readouts and minimal assay bundles.","authors":"Myeongwoo Jung, Seongho Cha, Eun Kyung Lee","doi":"","DOIUrl":"","url":null,"abstract":"Cellular senescence is an irreversible program of cell-cycle arrest that accumulates with age, contributing to chronic inflammation and various age-related diseases. A key feature of senescence paradigms is mitochondrial dysfunction, which involves not just a single defect but a series of coordinated changes in bioenergetics, redox homeostasis, mitochondrial quality control, and organelle interaction. Senescent cells often display a \"quantity-quality imbalance\" in their mitochondria: while the mitochondrial mass may increase, their efficiency in oxidative phosphorylation decreases, leading to a destabilized membrane potential (ΔΨm) and elevated levels of mitochondrial reactive oxygen species (mtROS). These interrelated changes can exacerbate senescence through persistent stress signaling, impaired turnover of damaged mitochondrial components, and alterations in organelle contacts, such as those between endoplasmic reticulum (ER) and mitochondria, and between mitochondria and lysosomes. Given that these phenotypes differ depending on cell type, triggering factors, and timing, no single assay can adequately define senescenceassociated mitochondrial dysfunction. In this review, we present practical, complementary strategies that include extracellular flux-based respiration profiling, ATP output measurement, ΔΨm and ROS assessments, flux-based mitophagy reporters, quantitative network imaging, and contact-site assays. We propose minimal assay bundles that allow for a thorough multidimensional analysis. By establishing standardized, orthogonal measures of mitochondrial quantity and quality, we aim to enhance mechanistic understanding and facilitate the rational evaluation of mitochondria-targeted senolytic and senomorphic therapies. [BMB Reports 2026; 59(3): 177-186].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"177-186"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HERV-R (ERV3-1) Env gene knockout reduces invasion, migration, and tumor growth in DLD1 colon cancer cells. HERV-R (ERV3-1) Env基因敲除可减少DLD1结肠癌细胞的侵袭、迁移和肿瘤生长。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-01

Min-Hye Kim, Eun-Ji Ko, Hyojin An, Seongsoo Choi, Heui-Soo Kim, Sun-Hee Leem, Hee-Jae Cha

{"title":"HERV-R (ERV3-1) Env gene knockout reduces invasion, migration, and tumor growth in DLD1 colon cancer cells.","authors":"Min-Hye Kim, Eun-Ji Ko, Hyojin An, Seongsoo Choi, Heui-Soo Kim, Sun-Hee Leem, Hee-Jae Cha","doi":"","DOIUrl":"","url":null,"abstract":"The human genome contains sequences derived from endogenous retroviruses (HERVs), which constitute approximately 8% of chromosomal DNA. Most HERVs are currently inactive and noninfectious due to recombination, deletion, and mutation after integration into the host genome. However, recent studies have implicated HERVs as mutagens of intracellular genes, contributing to autoimmune diseases and tumors. Several studies have shown a significant association between HERVs and certain cancers. We focused on knocking out the HERV-R (ERV3-1) env gene in the DLD1 colon cancer cell line. A 208-bp deletion was confirmed by genomic PCR and DNA sequencing. As a result, HERV-R env gene expression was significantly lower in DLD1 HERV-R knockout (HERV-R KO) cells compared to control cells at both RNA and protein levels. Additionally, the invasion and migration abilities of HERV-R KO cells were significantly reduced. In vivo experiments on mice injected with HERV-R KO cells showed smaller tumor sizes compared to mice injected with control cells, suggesting that HERV-R env plays an important role in tumor growth. Further mRNA-seq analysis identified genes associated with cell invasion and migration. The STRING tool, which analyzes gene correlations, confirmed that HERV-R is linked to genes involved in cancer proliferation, migration, and invasion in colon cancer. This study suggests that the expression of the HERV-R env gene influences the tumorigenic properties of colon cancer, providing valuable evidence for potential clinical studies in colon cancer patients. [BMB Reports 2026; 59(3): 201-207].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"201-207"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming. 小脑上调通过线粒体功能重编程克服多发性骨髓瘤的沙利度胺耐药性。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-03-01

Jubert Marquez, Nammi Park, Jae Hyeog Choi, Maria Victoria Faith Garcia, Jessa Flores, Bayalagmaa Nyamaa, Jung Eun Seol, Hyoung Kyu Kim, Myung Geun Shin, Sae Gwang Park, Jin Han

{"title":"Cereblon upregulation overcomes thalidomide resistance in multiple myeloma through mitochondrial functional reprogramming.","authors":"Jubert Marquez, Nammi Park, Jae Hyeog Choi, Maria Victoria Faith Garcia, Jessa Flores, Bayalagmaa Nyamaa, Jung Eun Seol, Hyoung Kyu Kim, Myung Geun Shin, Sae Gwang Park, Jin Han","doi":"","DOIUrl":"","url":null,"abstract":"Patients with multiple myeloma develop resistance to thalidomide during therapy, and the mechanisms to counteract thalidomide resistance remain elusive. Here, we explored the interaction between cereblon and mitochondrial function to mitigate thalidomide resistance in multiple myeloma. Measurements of cell viability, ATP production, mitochondrial membrane potential, mitochondrial ROS, and protein expression via western blotting were conducted in vitro using KSM20 and KMS26 cells to assess the impact of thalidomide on multiple myeloma. An in vivo analysis using xenografted multiple myeloma cells in BALB/c nude mice revealed that KMS20 cells were resistant to thalidomide, whereas KMS26 cells were sensitive. Overexpression of CRBN in a KMS20 xenograft model reversed its resistance to thalidomide, reduced tumor growth, and significantly extended the survival rate of the mice. Overexpression of CRBN in thalidomide-resistant KMS20 cells during thalidomide treatment led to effective cell death through the modulation of mitochondrial function and protein expression, mediated by AMPKα1 signaling. Conversely, both genetic and pharmacological knockdowns of CRBN rendered KMS26 cells resistant to thalidomide, indicating that CRBN level modulation directly influences mitochondrial functions. These findings propose that targeting cereblon offers a promising strategy in overcoming thalidomide resistance in multiple myeloma through mitochondrial reprogramming. [BMB Reports 2026; 59(3): 193-200].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"193-200"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FBXL18 activating AKT/CCND1 signaling pathway mediates radioresistance in esophageal squamous cell carcinoma. FBXL18激活AKT/CCND1信号通路介导食管鳞状细胞癌的放射耐药。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-02-09

Yahui Kang, Ning Ge, Xiaolong Yuan, Bihong Zhan, Hongbo Zhang

{"title":"FBXL18 activating AKT/CCND1 signaling pathway mediates radioresistance in esophageal squamous cell carcinoma.","authors":"Yahui Kang, Ning Ge, Xiaolong Yuan, Bihong Zhan, Hongbo Zhang","doi":"","DOIUrl":"","url":null,"abstract":"F-box and leucine-rich repeat protein 18 (FBXL18) is closely associated with cancer progression. However, its role in regulating the radioresistance of esophageal squamous cell carcinoma (ESCC) remains unclear. Radioresistant ESCC cells were developed using fractional doses of X-ray irradiation, and validated via cell counting kit-8 (CCK-8) assay. The sensitivity of these radioresistant cells to radiotherapy was also assessed using CCK-8. The expression levels of FBXL18 and Cyclin D1 (CCND1) were analyzed through Western blotting. RNA interference (RNAi) technology was employed to investigate whether silencing FBXL18 could reduce ESCC radioresistance and inhibit the AKT/CCND1 signaling pathway. Co-immunoprecipitation and Western blotting were used to evaluate the polyubiquitination of AKT. Radioresistant ESCC cells were successfully established, and FBXL18 expression was significantly elevated in these cells. Increased levels of phosphorylated AKT (p-AKT) and CCND1 were also observed. Silencing FBXL18 notably reduced the radioresistance of ESCC cells and decreased p-AKT and CCND1 expression levels. Also, FBXL18 was found to interact with AKT, promoting its K63-linked polyubiquitination, and activating the AKT/CCND1 signaling pathway. FBXL18 interacts with AKT and facilitates its K63-linked polyubiquitination, thereby activating AKT/CCND1 signaling while maintaining the radioresistance of ESCC cells.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141281","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}

引用次数: 0

Multifaceted roles of casein kinase 1 in health and disease: beyond cancer. 酪蛋白激酶1在健康和疾病中的多方面作用：超越癌症。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-02-09

Semi Kim, Ji Hoon Oh

{"title":"Multifaceted roles of casein kinase 1 in health and disease: beyond cancer.","authors":"Semi Kim, Ji Hoon Oh","doi":"","DOIUrl":"","url":null,"abstract":"Casein kinase 1 (CK1) enzymes, a family of serine/threoninespecific protein kinases, are remarkably conserved throughout evolution and exhibit diverse functionalities across eukaryotic species. While initially characterized by their role in casein (a type of milk protein) phosphorylation, subsequent investigations have unveiled their extensive involvement in fundamental biological processes, including cell division, maintenance of DNA integrity, programmed cell death, and the intricate regulation of gene transcription. Furthermore, CK1 significantly influences circadian rhythm mechanisms, highlighting its systemic regulatory importance. In mammals, multiple CK1 isoforms have been identified, each contributing to both physiological functions and various disease states. Dysregulation of CK1 activity is consistently associated with oncogenesis, where it promotes tumor cell proliferation, survival, metastasis, and resistance to therapeutic interventions. Emerging evidence also points to the critical relevance of CK1 in non-malignant conditions, such as neurodegenerative diseases, metabolic syndromes, and immune dysfunctions. In these conditions, CK1 often mediates pathogenic signaling through aberrant phosphorylation and the disruption of temporal gene expression. This review aims to re-examine the CK1 family as a versatile regulator that interacts with various pathological conditions, extending beyond its traditional classification as merely a signaling kinase. We provide an overview of the structural and functional properties of CK1 isoforms, summarize their relevance across a range of diseases, and explore novel possibilities for therapeutic interventions targeting this kinase family. Moreover, by reviewing the current understanding of CK1, we search for a new perspective on its role in maintaining cellular balance and its contribution to disease mechanisms, thereby proposing novel avenues for future research.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141324","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}

引用次数: 0

Silencing of E6/E7 proteins of HPV-16 in the CaCx cell line upregulate the expression of POTE-Paralogs. 在CaCx细胞系中，沉默HPV-16的E6/E7蛋白可上调pote - parogs的表达。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-02-09

Niranjan Kumar, Rashmi Rani Sahu, Amrita Singh, Akanksha Vyas, Saurabh Kumar, Prerona Das, Monika Sachdev

{"title":"Silencing of E6/E7 proteins of HPV-16 in the CaCx cell line upregulate the expression of POTE-Paralogs.","authors":"Niranjan Kumar, Rashmi Rani Sahu, Amrita Singh, Akanksha Vyas, Saurabh Kumar, Prerona Das, Monika Sachdev","doi":"","DOIUrl":"","url":null,"abstract":"POTE proteins are known to be expressed in tissues such as normal prostate, placenta, ovary, testis, and embryo, and are collectively referred to as POTE-family proteins based on this organ-specific expression. The POTE gene spans 32 kb on chromosome 21q11.2, although its homologous genes are distributed across eight different chromosomes. POTEE, as a member of the POTE family, has been identified as a Cancer Germline Antigen (CGA) across several cancer types including Colorectal, Pancreatic, Breast, Liver, and Lung cancers. This study aims to elucidate the role of POTE-Paralogs (POTEE & POTEF) as CGA markers in Cervical Cancer (CaCx). Over 90% of CaCx cases are associated with persistent infection by high-risk HPV (HR-HPV); the E6 and E7 oncoproteins of HPV contribute to carcinogenesis through the degradation or inactivation of tumor suppressor proteins p53 and pRB, leading to uncontrolled cell proliferation. Consequently, HPV-positive cervical cancer cell lines HeLa and CaSki lack detectable expression of p53, and the expression of POTE-Paralogs is also markedly decreased, while the HPV-negative CaCx cell line C-33A exhibits high p53 expression correlated with marked upregulation of POTE-Paralogs. Treatment of C-33A cells with a p53-specific inhibitor reduced POTE-Paralogs expression. Conversely, restoring p53 expression in CaSki cells with the chemotherapeutic agent Doxorubicin resulted in increased expression of POTE-Paralogs. Furthermore, silencing of E6/E7 in CaSki cells led to restoration of both p53 and pRB expression, as well as an increase in POTEE & POTEF levels.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141343","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}

引用次数: 0

FOXO6 activation promotes hepatic steatosis via PPARα inhibition in aged male rats. FOXO6激活通过抑制PPARα促进老年雄性大鼠肝脏脂肪变性。

IF 3.3 3区生物学

BMB Reports Pub Date : 2026-02-09

Yeong Un Kim, Ji Hyun Park, Dae Hyun Kim

{"title":"FOXO6 activation promotes hepatic steatosis via PPARα inhibition in aged male rats.","authors":"Yeong Un Kim, Ji Hyun Park, Dae Hyun Kim","doi":"","DOIUrl":"","url":null,"abstract":"Aging contributes to hepatic steatosis by increasing de novo lipogenesis. The Forkhead box O6 (FOXO6) transcription factor links insulin signaling to lipid metabolism. Activated FOXO6 induces hyperlipidemia and decreases peroxisome proliferator-activated receptor alpha (PPARα), thereby promoting hepatic lipogenesis. In this paper, we describe the role of FOXO6 in hepatic steatosis in aged male rats and liver cells, and examine the relationship between FOXO6 and PPARα, and the functional consequences of their altered interaction. We find that FOXO6 induces lipid accumulation by inhibiting PPARα in aged male rat livers. Our data show that AKT signaling negatively regulates FOXO6-induced hepatic lipid accumulation, and that a key β-oxidation gene, PPARα, is decreased in aged livers. We further demonstrate that FOXO6 activation decreases PPARα expression and increases lipid accumulation. Furthermore, interaction between FOXO6 and PPARα promotes hepatic steatosis in aged males. Also, high glucose upregulates Foxo6, reduces β-oxidation gene expression, and increases cellular TG-mediated lipid accumulation. Transcriptional activation of FOXO6 by aging and high glucose cause lipid accumulation by downregulating PPARα and hyperglycemia-responsive genes in aged male rats and liver cell cultures. We provide evidence that age-related insulin resistance suppresses β-oxidation through interaction between FOXO6 and PPARα, thereby promoting hepatic lipid accumulation in aged male rats.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141339","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}

引用次数: 0