American journal of physiology. Cell physiology最新文献_第4页

Transcriptional regulation of olfactory receptor OR51B5 by the TBX6. TBX6 对嗅觉受体 OR51B5 的转录调控。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00464.2024

Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park

{"title":"Transcriptional regulation of olfactory receptor OR51B5 by the TBX6.","authors":"Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park","doi":"10.1152/ajpcell.00464.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00464.2024","url":null,"abstract":"Olfactory receptors (ORs) are G protein-coupled receptors primarily expressed in olfactory tissue, facilitating the perception of odors. Interestingly, they have also been detected in non-olfactory tissues such as the skin, where they regulate processes like collagen synthesis. This study aimed to analyze the promoter of the OR family 51 subfamily B member 5 (OR51B5) and identify the transcription factors that bind to it to understand the potential regulatory mechanisms for OR51B5 expression. We examined the promoter region spanning 2,000 base pairs upstream of the transcription start site and conducted a deletion analysis, revealing that the core promoter encompasses the region from -153 to -111 base pairs. A luciferase assay using various candidate transcription factors showed that the overexpression or knockdown of T-Box Transcription Factor 6 (TBX6) significantly regulated OR51B5 promoter activity, while other candidate transcription factors had no significant effect. Additionally, we validated TBX6 binding to the OR51B5 promoter using site-directed mutation and electrophoretic mobility shift assays. This study is the first to uncover the role of TBX transcription factors in regulating OR gene expression in mammals, which may have implications for treating related disorders.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492915","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}

引用次数: 0

The Contribution of the Novel CLTC-VMP1 Fusion Gene to Autophagy Regulation and Energy Metabolism in Cisplatin-Resistant Osteosarcoma. 新型 CLTC-VMP1 融合基因对顺铂耐药骨肉瘤自噬调控和能量代谢的贡献

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00302.2024

Zhiwei Tao, Pingan Zou, Zhengxu Yang, Tao Xiong, Zhi Deng, Qinchan Chen

{"title":"The Contribution of the Novel CLTC-VMP1 Fusion Gene to Autophagy Regulation and Energy Metabolism in Cisplatin-Resistant Osteosarcoma.","authors":"Zhiwei Tao, Pingan Zou, Zhengxu Yang, Tao Xiong, Zhi Deng, Qinchan Chen","doi":"10.1152/ajpcell.00302.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00302.2024","url":null,"abstract":"Osteosarcoma (OS) is a highly malignant tumor, and chemotherapy resistance is a major challenge in the treatment of this disease. This study aims to explore the role of the CLTC-VMP1 gene fusion in the mechanism of chemotherapy resistance in OS and investigate its molecular mechanisms in mediating energy metabolism reprogramming by regulating autophagy and apoptosis balance. Using single-cell transcriptome analysis, the heterogeneity of OS cells and their correlation with resistance to platinum drugs were revealed. Cisplatin-resistant cell lines were established in human OS cell lines for subsequent experiments. Based on transcriptomic analysis, the importance of VMP1 in chemotherapy resistance was confirmed. Lentiviral vectors overexpressing or interfering with VMP1 were used, and it was observed that inhibiting VMP1 could reverse cisplatin resistance, promote cell apoptosis, and inhibit autophagy, as well as mitochondrial respiration and glycolysis. Furthermore, the presence of CLTC-VMP1 gene fusion was validated, and its ability to regulate autophagy and apoptosis balance, promote mitochondrial respiration, and glycolysis was demonstrated. Mouse model experiments further confirmed the promoting effect of CLTC-VMP1 on tumor growth and chemotherapy resistance. In summary, the CLTC-VMP1 gene fusion mediates energy metabolism reprogramming by regulating autophagy and apoptosis balance, which promotes chemotherapy resistance in OS.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492912","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}

引用次数: 0

Transcriptional Analysis of Cancer Cachexia: Conserved and Unique Features Across Pre-Clinical Models and Biological Sex. 癌症痛症的转录分析：跨临床前模型和生物性别的保守和独特特征

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00647.2024

Francielly Morena, Ana Regina Cabrera, Ronald G Jones Iii, Eleanor R Schrems, Ruqaiza Muhyudin, Tyrone A Washington, Kevin A Murach, Nicholas P Greene

{"title":"Transcriptional Analysis of Cancer Cachexia: Conserved and Unique Features Across Pre-Clinical Models and Biological Sex.","authors":"Francielly Morena, Ana Regina Cabrera, Ronald G Jones Iii, Eleanor R Schrems, Ruqaiza Muhyudin, Tyrone A Washington, Kevin A Murach, Nicholas P Greene","doi":"10.1152/ajpcell.00647.2024","DOIUrl":"10.1152/ajpcell.00647.2024","url":null,"abstract":"Studies suggest heterogeneity in cancer cachexia (CC) among models and biological sexes, yet examinations comparing models and sexes are scarce. We compared the transcriptional landscape of skeletal muscle across murine CC models and biological sexes during early and late CC. Global gene expression analyses were performed on gastrocnemius (LLC-Lewis Lung Carcinoma), quadriceps (KPC-pancreatic), and tibialis anterior (C26-colorectal and ApcMin/+) muscles across biological sexes. Differentially expressed genes (DEGs) were identified using an adj-p-value of <0.05, followed by pathway and computational cistrome analyses. Integrating all controls, early, and late-stage of all models and sexes revealed up to 68% of DEGs and pathways were enriched at early and late CC, indicating a conserved transcriptional profile during CC development. Comparing DEGs and pathways within sexes and across models, in early-CC, the transcriptional response was highly heterogeneous. At late-stage, 11.5% of upregulated and 10% of downregulated genes were shared between models in males, while 18.9% of upregulated and 7% of downregulated DEGs were shared in females. Shared DEGs were enriched in proteasome and mitophagy/autophagy pathways (upregulated), and downregulation of energy metabolism pathways in males only. Between sexes, though proportion of shared DEGs was low (<16%), similar pathway enrichment was observed, including proteasome and mitophagy at late-stage CC. In early-CC, Osmr upregulation was the only commonality across all models and sexes, while CLOCK and ARNTL/BMAL1 were predicted transcriptional factors associated with dysregulations in all three male models. This study highlights sex and model differences in CC progression and suggests conserved transcriptional changes as potential therapeutic targets.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492914","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}

引用次数: 0

Ion Channel Piezo1 Induces Ferroptosis of Trabecular Meshwork Cells: A Novel Observation in the Pathogenesis in Primary Open Angle Glaucoma. 离子通道 Piezo1 可诱导小梁网状结构细胞铁突变：原发性开角型青光眼发病机制的新发现

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00173.2024

Kexin Liu, Jing Xu, Rufei Yang, Feng Wang, Ying Su

{"title":"Ion Channel Piezo1 Induces Ferroptosis of Trabecular Meshwork Cells: A Novel Observation in the Pathogenesis in Primary Open Angle Glaucoma.","authors":"Kexin Liu, Jing Xu, Rufei Yang, Feng Wang, Ying Su","doi":"10.1152/ajpcell.00173.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00173.2024","url":null,"abstract":"Purpose: This study aims to elucidate the role of Piezo1, a mechanosensitive molecule, in trabecular meshwork cells (TMCs) in the context of Primary Open Angle Glaucoma (POAG), a leading cause of irreversible visual impairment. Dysfunction of the trabecular meshwork (TM) is a key factor in the elevated intraocular pressure (IOP) observed in POAG, yet the specific mechanisms leading to TM dysfunction are not fully understood.Methods: We performed cell stretching on human trabecular meshwork cells (HTMCs) and pharmacologically activated HTMCs with Yoda1 to study the role of Piezo1 in HTMCs. We focused on assessing cell viability, mitochondrial changes, lipid peroxidation, and the expression of ferroptosis-related targets such as acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4).Results: Cell stretching induces ferroptosis in HTMCs, and this phenomenon is reversed by Piezo1 knockdown. Additionally, pharmacological activation of Piezo1 also leads to ferroptosis in HTMCs. Furthermore, inhibiting the JNK/p38 signaling pathway was found to mitigate the ferroptotic response induced by Yoda1, thereby confirming that Piezo1 induces ferroptosis in TMCs through this pathway. Notably, our experiments suggest that Yoda1 may trigger ferroptosis in the TM of mouse eyes.Conclusions: Our findings demonstrate that the Piezo1 pathway is a crucial mediator of ferroptosis in TMCs, providing new insights into the pathogenic mechanisms of glaucoma, particularly POAG. This study highlights the potential of targeting the Piezo1 pathway as a therapeutic approach for mitigating TM dysfunction and managing POAG.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492907","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}

引用次数: 0

The mechanical journey of primordial germ cells. 原始生殖细胞的机械之旅

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00404.2024

Malhar Chitnis, Xu Gao, Jennifer Marlena, Andrew Holle

{"title":"The mechanical journey of primordial germ cells.","authors":"Malhar Chitnis, Xu Gao, Jennifer Marlena, Andrew Holle","doi":"10.1152/ajpcell.00404.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00404.2024","url":null,"abstract":"Primordial germ cells (PGCs) are the earliest progenitors of germline cells of the gonads in animals. The tissues that arise from primordial germ cells give rise to the male as well as female gametes and are thus responsible for transmitting genetic information to subsequent generations. Their development from single cells to fully formed tissues has thus been of great importance. In most higher animals, PGCs are initially specified at a site away from the gonads. They then migrate across multiple tissue contexts to reach a mesodermal mass of cells called the genital ridge, where they associate with somatic cells to form the sex-specific reproductive organs. This migratory behavior has been studied extensively to identify the various tissues PGCs interact with and how this might affect their development. A crucial point overlooked by classical studies has been the physical environment experienced by PGCs as they migrate and the mechanical challenges they might encounter. It has long been understood that migrating cells can sense and adapt to physical forces around them via a variety of mechanisms. Studies have also shown that these mechanical signals can guide stem cell fate. In this review, we summarize the mechanical microenvironment of migrating PGCs in different organisms. We describe how cells can adapt to this environment and how this adaptation can influence cell fate. We propose that mechanical signals play a crucial role in normal development of the germline and shed light on this unexplored area of developmental biology.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492913","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}

引用次数: 0

Molecular mapping of KCNE4-dependent regulation of Kv1.3. KCNE4 依赖性调控 Kv1.3 的分子图谱。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-28 DOI: 10.1152/ajpcell.00499.2024

Daniel Sastre, Magali Colomer-Molera, Sara R Roig, Angela de Benito-Bueno, Paula G Socuellamos, Gregorio Fernandez-Ballester, Carmen Valenzuela, Antonio Felipe

{"title":"Molecular mapping of KCNE4-dependent regulation of Kv1.3.","authors":"Daniel Sastre, Magali Colomer-Molera, Sara R Roig, Angela de Benito-Bueno, Paula G Socuellamos, Gregorio Fernandez-Ballester, Carmen Valenzuela, Antonio Felipe","doi":"10.1152/ajpcell.00499.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00499.2024","url":null,"abstract":"The voltage-gated potassium channel Kv1.3 plays a crucial role in the immune system response. In leukocytes, the channel is coexpressed with the dominant negative regulatory subunit KCNE4, which associates with Kv1.3 to trigger intracellular retention and accelerating C-type inactivation of the channel. Previous research has demonstrated that the main association between these proteins occurs through both C-termini. However, these data fail to fully elucidate the KCNE4-dependent modulation of channel kinetics. In the present study, we analyzed the contribution of each KCNE4 domain to the modulation of Kv1.3. Our results further confirmed that the C-terminus of KCNE4 is the main determinant involved in the association-triggered intracellular retention of the channel. Moreover, interactions throughout the transmembrane region were also observed. Both the C-terminus and, especially, the transmembrane domain of KCNE4 accentuated the C-type inactivation of Kv1.3. Our data provide, for the first time, the molecular effects that a KCNE peptide, such as KCNE4, exerts on a Shaker channel, such as Kv1.3. Our results pave the way for understanding the molecular mechanisms underlying potassium channel modulation and suggest that KCNE4 participates in the conformational rearrangement of the Kv1.3 architecture, altering the C-type inactivation of the channel.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492909","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}

引用次数: 0

ITGA3 participates in the pathogenesis of recurrent spontaneous abortion by downregulating ULK1-mediated autophagy to inhibiting trophoblast function. ITGA3通过下调ULK1介导的自噬抑制滋养细胞功能，参与复发性自然流产的发病机制。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-22 DOI: 10.1152/ajpcell.00563.2024

Rui Qi Wang, Fangfang Dai, Zhimin Deng, Lujia Tang, Hua Liu, Liangbin Xia, Yanxiang Cheng

{"title":"ITGA3 participates in the pathogenesis of recurrent spontaneous abortion by downregulating ULK1-mediated autophagy to inhibiting trophoblast function.","authors":"Rui Qi Wang, Fangfang Dai, Zhimin Deng, Lujia Tang, Hua Liu, Liangbin Xia, Yanxiang Cheng","doi":"10.1152/ajpcell.00563.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00563.2024","url":null,"abstract":"Recurrent spontaneous abortion (RSA) is a significant challenge encountered by couples of reproductive ages, with inadequate trophoblast invasion identified as a primary factor in RSA pathogenesis. However, the precise molecular mechanisms through which trophoblast cells dysfunction leads to RSA remain incompletely understood. Research has highlighted the critical role of integrins in embryo implantation and development. While integrin α-3 (ITGA3) is recognized for its promotion of invasion in cancer cells, its involvement in miscarriage remains poorly characterized. This investigation initially assessed ITGA3 expression in villous tissues obtained from RSA patients and induced abortion patients. The findings demonstrated a notable reduction in ITGA3 levels in the villous tissues of RSA patients compared control group. Subsequent in vitro analyses indicated that ITGA3 knockdown inhibited the migration, invasion, and proliferation of trophoblast cells. Through RNA sequencing and subsequent experimentation, it was revealed that ITGA3 regulated ULK1-mediated autophagy to influence trophoblast cells invasion, migration, and proliferation. Furthermore, utilizing a miscarriage animal model, the diminished expression of ITGA3 and ULK1 in the placentas of RSA mice was confirmed. In conclusion, the study findings suggest that the downregulation of ITGA3 suppresses ULK1 expression, consequently impeding autophagy to initiation and impeding trophoblast cells invasion and migration, thereby contributing to the pathological progression of RSA.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492908","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}

引用次数: 0

Targeting the gut and tumor microbiome in cancer resistance. 在抗癌过程中瞄准肠道和肿瘤微生物组。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-22 DOI: 10.1152/ajpcell.00201.2024

Sona Ciernikova, Aneta Sevcikova, Michal Mego

{"title":"Targeting the gut and tumor microbiome in cancer resistance.","authors":"Sona Ciernikova, Aneta Sevcikova, Michal Mego","doi":"10.1152/ajpcell.00201.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00201.2024","url":null,"abstract":"Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironment and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a pro-apoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pre-treatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492910","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}

引用次数: 0

Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress. 健康血浆脂质体特征取决于性别、年龄、体重指数和避孕药具，但与感知到的压力无关。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-22 DOI: 10.1152/ajpcell.00630.2024

Lisa Hahnefeld, Juliane Hackel, Sandra Trautmann, Carlo Angioni, Yannick Schreiber, Robert Gurke, Dominique Thomas, Sabine Wicker, Gerd Geisslinger, Irmgard Tegeder

{"title":"Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress.","authors":"Lisa Hahnefeld, Juliane Hackel, Sandra Trautmann, Carlo Angioni, Yannick Schreiber, Robert Gurke, Dominique Thomas, Sabine Wicker, Gerd Geisslinger, Irmgard Tegeder","doi":"10.1152/ajpcell.00630.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00630.2024","url":null,"abstract":"Perceived stress is thought to contribute to the pathogenesis of metabolic, vascular, mental, and immune diseases, with different susceptibilities in women and men. The present study investigated if and how perceived stress and/or demographic variables including sex, age, body mass index, regular prescription drugs, occasional analgesics, or dietary supplements manifested in plasma lipidomic profiles, obtained by targeted and untargeted mass spectrometry analyses. The study included 217 healthy women and 108 healthy men, aged 18-68 years, who were recruited in a 2:1 female:male ratio to account for women with/without contraceptives. As expected, dehydroepiandrosterone sulfate (DHEAS) and ceramides were higher in men than women, and DHEAS decreased with age, while ceramides increased. Contrary to expectations, neither DHEAS nor ceramides were associated with perceived stress (PSQ30 questionnaire), which was however, associated with BMI in men, but not in women. None of the lipid species or classes showed a similar \"age X sex X BMI\" interaction, but the endocannabinoid palmitoylethanolamide (PEA) correlated with BMI and hypertension. Independent of perceived stress, lysophosphatidylcholines (LPCs) were lower in women than men, whereas LPC metabolites, lysophosphatidic acids (LPAs), were higher in women. The LPA:LPC ratio was particularly high in women using oral contraceptives suggesting a strong hormone-induced extracellular conversion of LPCs to LPAs, which is catalyzed by the phospholipase D, autotaxin. The results reveal complex sex differences in perceived stress and lipidomic profiles, the latter being exacerbated by contraceptive use, but perceived stress and lipids were not directly correlated.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492906","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}

引用次数: 0

TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy. TFEB 信号促进 NLRP3 的自噬降解，从而减轻糖尿病脑病的神经炎症。

IF 5 2区生物学

American journal of physiology. Cell physiology Pub Date : 2024-10-22 DOI: 10.1152/ajpcell.00322.2024

Yijia Lin, Lizhen Cheng, Yixin Chen, Wei Li, Qihao Guo, Ya Miao

{"title":"TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.","authors":"Yijia Lin, Lizhen Cheng, Yixin Chen, Wei Li, Qihao Guo, Ya Miao","doi":"10.1152/ajpcell.00322.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00322.2024","url":null,"abstract":"Diabetic encephalopathy (DE), a neurological complication of diabetes mellitus, has an unclear etiology. Shreds of evidence show that the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome-induced neuroinflammation and transcription factor EB (TFEB)-mediated autophagy impairment may take part in DE development. The crosstalk between these two pathways and their contribution to DE remains to be explored. A mouse model of type 2 diabetes mellitus (T2DM) exhibiting cognitive dysfunction was created, along with high glucose (HG) cultured BV2 cells. Following, 3-methyladenine (3-MA) and rapamycin were utilized to modulate autophagy. To evaluate the potential therapeutic benefits of TFEB in DE, we overexpressed and knocked down TFEB in both mice and cells. Autophagy impairment and NLRP3 inflammasome activation were noticed in T2DM mice and HG-cultured BV2 cells. The inflammatory response caused by NLRP3 inflammasome activation was decreased by rapamycin-induced autophagy enhancement, while 3-MA treatment further deteriorated it. Nuclear translocation and expression of TFEB were hampered in HG-cultured BV2 cells and T2DM mice. Exogenous TFEB overexpression boosted NLRP3 degradation via autophagy, which in turn alleviated microglial activation as well as ameliorated cognitive deficits and neuronal damage. Additionally, TFEB knockdown exacerbated neuroinflammation by decreasing autophagy-mediated NLRP3 degradation. Our findings have unraveled the pathogenesis of a previously underappreciated disease, implying that the activation of NLRP3 inflammasome and impairment of autophagy in microglia are significant etiological factors in the DE. The TFEB-mediated autophagy pathway can reduce neuroinflammation by enhancing NLRP3 degradation. This could potentially serve as a viable and innovative treatment approach for DE.","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492911","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}

引用次数: 0