FASEB bioAdvances最新文献_第8页

Akkermansia muciniphila promotes testosterone-mediated hair growth inhibition in mice Akkermansia muciniphila 促进睾酮介导的小鼠毛发生长抑制作用

IF 2.7

FASEB bioAdvances Pub Date : 2023-10-25 DOI: 10.1096/fba.2023-00056

Eunyoung Lee, Daedong Kim, Hyo-Deok Seo, Jeong-Hoon Hahm, Jae-Gu Seo, Sang-Nam Lee, Do-Hak Kim, Jiyun Ahn, Chang Hwa Jung

{"title":"Akkermansia muciniphila promotes testosterone-mediated hair growth inhibition in mice","authors":"Eunyoung Lee, Daedong Kim, Hyo-Deok Seo, Jeong-Hoon Hahm, Jae-Gu Seo, Sang-Nam Lee, Do-Hak Kim, Jiyun Ahn, Chang Hwa Jung","doi":"10.1096/fba.2023-00056","DOIUrl":"10.1096/fba.2023-00056","url":null,"abstract":"The beneficial effects of Akkermansia muciniphila (Akk) on gut health and inflammation reduction have been demonstrated; however, scientific evidence of hair growth enhancement by Akk has not been reported. Therefore, this study was undertaken to investigate the effect of Akk on improving testosterone-mediated hair growth inhibition. Hair growth inhibition was induced through subcutaneous injection of testosterone into the shaved dorsal skin of C57BL/6 male mice. Live and pasteurized Akk were orally administered at a concentration of 1 × 108 colony-forming unit. After 5 weeks, hair length and skin tissues were analyzed. The live and pasteurized Akk significantly stimulated hair growth, countering the inhibitory effect of testosterone compared to the testosterone-alone group. Hematoxylin and eosin staining revealed a significant increase in hair follicle size in the Akk-treated group. An increase in β-catenin levels, which are associated with hair growth and cell cycle progression, was also observed. Moreover, the Akk-treated group exhibited increased levels of fibroblast growth factors, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21. However, no significant difference was observed between the live and pasteurized Akk groups. These results underscore the potential of live and pasteurized Akk in improving testosterone-mediated hair growth inhibition.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 12","pages":"521-527"},"PeriodicalIF":2.7,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135112305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRPV4-mediated Ca2+ deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons TRPV4 介导的 Ca2+ 失调通过 AKT/α-synuclein 通路导致多巴胺能神经元线粒体功能障碍

IF 2.7

FASEB bioAdvances Pub Date : 2023-10-11 DOI: 10.1096/fba.2023-00057

Xiao Sun, Jun Kong, Shuangshan Dong, Hiroki Kato, Hiroshi Sato, Yuta Hirofuji, Yosuke Ito, Lu Wang, Takahiro A. Kato, Michiko Torio, Yasunari Sakai, Shouichi Ohga, Satoshi Fukumoto, Keiji Masuda

{"title":"TRPV4-mediated Ca2+ deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons","authors":"Xiao Sun, Jun Kong, Shuangshan Dong, Hiroki Kato, Hiroshi Sato, Yuta Hirofuji, Yosuke Ito, Lu Wang, Takahiro A. Kato, Michiko Torio, Yasunari Sakai, Shouichi Ohga, Satoshi Fukumoto, Keiji Masuda","doi":"10.1096/fba.2023-00057","DOIUrl":"10.1096/fba.2023-00057","url":null,"abstract":"Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4-related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4-mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain-of-function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT-mediated α-synuclein (α-syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α-syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT-induced α-syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α-syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4-related disorders and related therapeutic strategies.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 12","pages":"507-520"},"PeriodicalIF":2.7,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136213609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From goal to outcome: Analyzing the progression of biomedical sciences PhD careers in a longitudinal study using an expanded taxonomy 从目标到结果：使用扩展的分类法，在一项纵向研究中分析生物医学博士职业生涯的进展。

IF 2.7

FASEB bioAdvances Pub Date : 2023-10-05 DOI: 10.1096/fba.2023-00072

Abigail M. Brown, Lindsay C. Meyers, Janani Varadarajan, Nicholas J. Ward, Jean-Philippe Cartailler, Roger G. Chalkley, Kathleen L. Gould, Kimberly A. Petrie

{"title":"From goal to outcome: Analyzing the progression of biomedical sciences PhD careers in a longitudinal study using an expanded taxonomy","authors":"Abigail M. Brown, Lindsay C. Meyers, Janani Varadarajan, Nicholas J. Ward, Jean-Philippe Cartailler, Roger G. Chalkley, Kathleen L. Gould, Kimberly A. Petrie","doi":"10.1096/fba.2023-00072","DOIUrl":"10.1096/fba.2023-00072","url":null,"abstract":"Biomedical sciences PhDs pursue a wide range of careers inside and outside academia. However, there is little data regarding how career interests of PhD students relate to the decision to pursue postdoctoral training or to their eventual career outcomes. Here, we present the career goals and career outcomes of 1452 biomedical sciences PhDs who graduated from Vanderbilt University between 1997 and 2021. We categorized careers using an expanded three-tiered taxonomy and flags that delineate key career milestones. We also analyzed career goal changes between matriculation and doctoral defense, and the reasons why students became more- or less-interested in research-intensive faculty careers. We linked students' career goal at doctoral defense to whether they did a postdoc, the duration of time between doctoral defense and the first non-training position, the career area of the first non-training position, and the career area of the job at 10 years after graduation. Finally, we followed individual careers for 10 years after graduation to characterize movement between different career areas over time. We found that most students changed their career goal during graduate school, declining numbers of alumni pursued postdoctoral training, many alumni entered first non-training positions in a different career area than their goal at doctoral defense, and the career area of the first non-training position was a good indicator of the job that alumni held 10 years after graduation. Our findings emphasize that students need a wide range of career development opportunities and career mentoring during graduate school to prepare them for futures in research and research-related professions.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 11","pages":"427-452"},"PeriodicalIF":2.7,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biological effects of air pollution on the function of human skin equivalents 空气污染对人体皮肤等同物功能的生物影响。

IF 2.7

FASEB bioAdvances Pub Date : 2023-10-03 DOI: 10.1096/fba.2023-00068

Wil J. Reynolds, Ndubuisi Eje, Paul Christensen, Wen-Hwa Li, Susan M. Daly, Ramine Parsa, Bhaven Chavan, Mark A. Birch-Machin

{"title":"Biological effects of air pollution on the function of human skin equivalents","authors":"Wil J. Reynolds, Ndubuisi Eje, Paul Christensen, Wen-Hwa Li, Susan M. Daly, Ramine Parsa, Bhaven Chavan, Mark A. Birch-Machin","doi":"10.1096/fba.2023-00068","DOIUrl":"10.1096/fba.2023-00068","url":null,"abstract":"The World Health Organization reports that 99% of the global population are exposed to pollution levels higher than the recommended air quality guidelines. Pollution-induced changes in the skin have begun to surface; however, the effects require further investigation so that effective protective strategies can be developed. This study aimed to investigate some of the aging-associated effects caused by ozone and particulate matter (PM) on human skin equivalents. Full-thickness skin equivalents were exposed to 0.01 μg/μL PM, 0.05 μg/μL PM, 0.3 ppm ozone, or a combination of 0.01 μg/μL PM and 0.3 ppm ozone, before skin equivalents and culture medium were harvested for histological/immunohistochemical staining, gene and protein expression analysis using qPCR, Western blotting, and ELISA. Markers include MMP-1, MMP-3, COL1A1, collagen-I, 4-HNE, HMGCR, and PGE2. PM was observed to induce a decrease in epidermal thickness and an enhanced matrix building phenotype, with increases in COL1A1 and an increase in collagen-I protein expression. By contrast, ozone induced an increase in epidermal thickness and was found to induce a matrix-degrading phenotype, with decreases in collagen-I gene/protein expression and increases in MMP-1 and MMP-3 gene/protein expression. Ozone was also found to induce changes in lipid homeostasis and inflammation induction. Some synergistic damage was also observed when combining ozone and 0.01 μg/μL PM. The results presented in this study identify distinct pollutant-induced effects and show how pollutants may act synergistically to augment damage; given individuals are rarely only exposed to one pollutant type, exposure to multiple pollutant types should be considered to develop effective protective interventions.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 11","pages":"470-483"},"PeriodicalIF":2.7,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Progranulin deficiency exacerbates cardiac remodeling after myocardial infarction 孕激素缺乏会加剧心肌梗死后的心脏重塑。

IF 2.7

FASEB bioAdvances Pub Date : 2023-09-20 DOI: 10.1096/fba.2023-00084

Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara

{"title":"Progranulin deficiency exacerbates cardiac remodeling after myocardial infarction","authors":"Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara","doi":"10.1096/fba.2023-00084","DOIUrl":"10.1096/fba.2023-00084","url":null,"abstract":"Myocardial infarction (MI) is a lethal disease that causes irreversible cardiomyocyte death and subsequent cardiovascular remodeling. We have previously shown that the administration of recombinant progranulin (PGRN) protects against myocardial ischemia and reperfusion injury. However, the post-MI role of PGRN remains unclear. In the present study, we investigated the effects of PGRN deficiency on cardiac remodeling after MI. Wild-type and PGRN-knockout mice were subjected to MI by ligation of the left coronary artery for histological, electrophysiological, and protein expression analysis. Cardiac macrophage subpopulations were analyzed by flow cytometry. Bone marrow-derived macrophages (BMDMs) were acquired and treated with LPS + IFN-γ and IL-4 to evaluate mRNA levels and phagocytic ability. PGRN expression was gradually increased in the whole heart at 1, 3, and 7 days after MI. Macrophages abundantly expressed PGRN at the border areas at 3 days post-MI. PGRN-knockout mice showed higher mortality, increased LV fibrosis, and severe arrhythmia following MI. PGRN deficiency increased the levels of CD206 and MerTK expression and macrophage infiltration in the infarcted myocardium, which was attributed to a larger subpopulation of cardiac CCR2+ Ly6Clow CD11b+ macrophages. PGRN-deficient BMDMs exhibited higher TGF-β, IL-4R, and lower IL-1β, IL-10 and increased acute phagocytosis following stimulation of LPS and IFN-γ. PGRN deficiency reduced survival and increased cardiac fibrosis following MI with the induction of abnormal subpopulation of cardiac macrophages early after MI, thereby providing insight into the relationship between properly initiating cardiac repair and macrophage polarization after MI.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 10","pages":"395-411"},"PeriodicalIF":2.7,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/c5/FBA2-5-395.PMC10551273.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple-negative breast cancer patients for potential biomarker development 分析癌症三阴性乳腺癌患者肿瘤和循环细胞外小泡中线粒体DNA突变的潜在生物标志物开发。

IF 2.7

FASEB bioAdvances Pub Date : 2023-09-08 DOI: 10.1096/fba.2023-00070

Kunwar Somesh Vikramdeo, Shashi Anand, Sarabjeet Kour Sudan, Paramahansa Pramanik, Seema Singh, Andrew K. Godwin, Ajay Pratap Singh, Santanu Dasgupta

{"title":"Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple-negative breast cancer patients for potential biomarker development","authors":"Kunwar Somesh Vikramdeo, Shashi Anand, Sarabjeet Kour Sudan, Paramahansa Pramanik, Seema Singh, Andrew K. Godwin, Ajay Pratap Singh, Santanu Dasgupta","doi":"10.1096/fba.2023-00070","DOIUrl":"10.1096/fba.2023-00070","url":null,"abstract":"Early detection and recurrence prediction are challenging in triple-negative breast cancer (TNBC) patients. We aimed to develop mitochondrial DNA (mtDNA)-based liquid biomarkers to improve TNBC management. Mitochondrial genome (MG) enrichment and next-generation sequencing mapped the entire MG in 73 samples (64 tissues and 9 extracellular vesicles [EV] samples) from 32 metastatic TNBCs. We measured mtDNA and cardiolipin (CL) contents, NDUFB8, and SDHB protein expression in tumors and in corresponding circulating EVs. We identified 168 nonsynonymous mtDNA mutations, with 73% (123/186) coding and 27% (45/168) noncoding in nature. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) was the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19%–38% TNBCs, which were detectable in the serum-derived EVs with 82% specificity. Overall, 38% of the metastatic tumor-signature mtDNA mutations were traceable in the EVs. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI-specific mtDNA mutational load was higher in women with African compared to European ancestry accompanied by an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p < 0.0001) content was recorded in both tumors and EVs along with an abundance of CL (p = 0.0001) content in the EVs. Aggressive tumor-signature mtDNA mutation detection and measurement of mtDNA and CL contents in the EVs bear the potential to formulate noninvasive early detection and recurrence prediction strategies.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 10","pages":"412-426"},"PeriodicalIF":2.7,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease 5/6肾切除和单侧输尿管梗阻模型的联合应用加速了慢性肾脏疾病远端器官纤维化的进展。

IF 2.7

FASEB bioAdvances Pub Date : 2023-08-19 DOI: 10.1096/fba.2023-00045

Kyoka Homma, Yuki Enoki, Sato Uchida, Kazuaki Taguchi, Kazuaki Matsumoto

{"title":"A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease","authors":"Kyoka Homma, Yuki Enoki, Sato Uchida, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1096/fba.2023-00045","DOIUrl":"10.1096/fba.2023-00045","url":null,"abstract":"Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6-nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis-related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor-β (TGF-β), a fibrosis-related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF-β levels. In agreement with the results of in vivo experiments, co-stimulation with IS, TGF-β, and macrophage-conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 10","pages":"377-394"},"PeriodicalIF":2.7,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of phytochelatins in human urine: Evidence for function in selenium disposition and protection against cadmium 人类尿液中植物螯合素的发现:硒处理和镉防护功能的证据

IF 2.7

FASEB bioAdvances Pub Date : 2023-08-12 DOI: 10.1096/fba.2023-00050

Zachery R. Jarrell, Ken H. Liu, Kristine K. Dennis, Xin Hu, Greg S. Martin, Dean P. Jones, Young-Mi Go

{"title":"Discovery of phytochelatins in human urine: Evidence for function in selenium disposition and protection against cadmium","authors":"Zachery R. Jarrell, Ken H. Liu, Kristine K. Dennis, Xin Hu, Greg S. Martin, Dean P. Jones, Young-Mi Go","doi":"10.1096/fba.2023-00050","DOIUrl":"10.1096/fba.2023-00050","url":null,"abstract":"This report identifies, for the first time, a phytochelatin compound, phytochelatin 2 [γ-E-C-γ-E-C-G], and related metabolites in human urine. Phytochelatins are metal-binding peptides produced by plants. They are present in nearly all human diets, due to their ubiquity in plants. The urinary concentration of phytochelatin 2 among 143 adults was in the low micromolar range, and phytochelatin 2 and its metabolites had differential correlations with urinary selenium and toxic metals. Activities of ingested phytochelatins are largely undescribed. Observed urinary metal interactions were investigated further in cell and animal models. Selenite reacted with phytochelatin to form a phytochelatin selenotrisulfide, and the preformed selenotrisulfide showed increased selenium uptake by renal proximal tubule cells. In vivo studies further showed that oral phytochelatin increased renal selenium content and decreased lung cadmium in mice. Presence of phytochelatin in human urine combined with its function in selenium and heavy metal distribution present a new route by which diet may influence metal disposition and bioavailability.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 9","pages":"367-375"},"PeriodicalIF":2.7,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/c1/FBA2-5-367.PMC10478506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 reactive oxygen species modify extracellular vesicles secretion rate 线粒体活性氧改变细胞外囊泡分泌速率

IF 2.7

FASEB bioAdvances Pub Date : 2023-06-27 DOI: 10.1096/fba.2023-00053

Mikkel Ø. Nørgård, Philip M. Lund, Nazmie Kalisi, Thomas L. Andresen, Jannik B. Larsen, Stefan Vogel, Per Svenningsen

{"title":"Mitochondrial reactive oxygen species modify extracellular vesicles secretion rate","authors":"Mikkel Ø. Nørgård, Philip M. Lund, Nazmie Kalisi, Thomas L. Andresen, Jannik B. Larsen, Stefan Vogel, Per Svenningsen","doi":"10.1096/fba.2023-00053","DOIUrl":"10.1096/fba.2023-00053","url":null,"abstract":"Extracellular vesicle (EV) secretion rate is stimulated by hypoxia that causes increased reactive oxygen species (ROS) production by the mitochondrial electron transport chain (ETC) and hypoxia-induced factor (HIF)-1 signaling; however, their contribution to the increased EV secretion rate is unknown. We found that the EV marker secretion rate in our EV reporter cell line CD9truc-EGFP was unaffected by the HIF-1α stabilizer roxadustat; yet, ETC stimulation by dichloroacetic acid (DCA) significantly increased EV secretion. The DCA-induced EV secretion was blocked by the antioxidant TEMPO and rotenone, an inhibitor of the ETC's Complex I. Under hypoxic conditions, the limited oxygen reduction impedes the ETC's Complex III. To mimic this, we inhibited Complex III with antimycin A, which increased ROS-dependent EV secretion. The electron transport between Complex I and III is accomplished by coenzyme Q created by the mevalonate pathway and tyrosine metabolites. Blocking an early step in the mevalonate pathway using pitavastatin augmented the DCA-induced EV secretion, and 4-nitrobenzoate—an inhibitor of the condensation of the mevalonate pathway with tyrosine metabolites—increased ROS-dependent EV secretion. Our findings indicate that hypoxia-mimetics targeting the ETC modify EV secretion and that ROS produced by the ETC is a potent stimulus for EV secretion.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 9","pages":"355-366"},"PeriodicalIF":2.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/25/FBA2-5-355.PMC10478507.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Two different isoforms of osteopontin modulate myelination and axonal integrity 两种不同的骨桥蛋白同种异构体调节髓鞘形成和轴突完整性

IF 2.7

FASEB bioAdvances Pub Date : 2023-06-17 DOI: 10.1096/fba.2023-00030

Gisela Nilsson, Amin Mottahedin, Aura Zelco, Volker M. Lauschke, C. Joakim Ek, Juan Song, Maryam Ardalan, Sha Hua, Xiaoli Zhang, Carina Mallard, Henrik Hagberg, Jianmei W. Leavenworth, Xiaoyang Wang

{"title":"Two different isoforms of osteopontin modulate myelination and axonal integrity","authors":"Gisela Nilsson, Amin Mottahedin, Aura Zelco, Volker M. Lauschke, C. Joakim Ek, Juan Song, Maryam Ardalan, Sha Hua, Xiaoli Zhang, Carina Mallard, Henrik Hagberg, Jianmei W. Leavenworth, Xiaoyang Wang","doi":"10.1096/fba.2023-00030","DOIUrl":"10.1096/fba.2023-00030","url":null,"abstract":"Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform-specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN-KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN-KO mice compared to control mice. Accordingly, adult OPN-KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin-related proteins. In contrast, neonatal oligodendrocytes from OLs-iOPN-KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs-iOPN-KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform-specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 8","pages":"336-353"},"PeriodicalIF":2.7,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/03/FBA2-5-336.PMC10405251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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