FASEB bioAdvances最新文献

{"title":"Ovomemolins: Egg-derived peptides that improved cognitive decline after oral administration in mice","authors":"Takanobu Nakajima,&nbsp;Maiko Shobako,&nbsp;Kentaro Kaneko,&nbsp;Atsushi Kurabayashi,&nbsp;Masaru Sato,&nbsp;Kousaku Ohinata","doi":"10.1096/fba.2023-00149","DOIUrl":"10.1096/fba.2023-00149","url":null,"abstract":"<p>Eggs not only contain all the molecules necessary to nurture new life but are also rich in nutrients such as high-quality protein. For example, epidemiologic studies have shown that egg intake is positively correlated with cognitive function. Thus, we specifically examined the effect of ovalbumin, a major protein present in egg whites, on cognitive function. First, we found that an orally administered enzymatic digest of ovalbumin improves cognitive function in mice fed a high-fat diet. Then, we narrowed down candidate peptides based on the prediction of peptide production according to enzyme-substrate specificity and comprehensive peptide analysis of the digest. We found that three peptides, namely ILPEY, LYRGGLEP, and ILELP, improve cognitive function after oral administration. We also showed that ILPEY, LYRGGLEP, and ILELP were present in the digest and named them ovomemolins A (OMA), B, and C, respectively. Notably, ovomemolins are the first peptides derived from egg whites that have been shown to improve cognitive function. The cognitive improvement induced by OMA, the most abundant of the peptides in the digest, was inhibited by methyllycaconitine, an antagonist of α7nAChR, which is known to be related to memory. These results suggest that OMA improves cognitive function through the acetylcholine system. After OMA administration, brain-derived neurotrophic factor (BDNF) mRNA expression and the number of 5-bromo-2′-deoxyuridine-positive cells suggested that OMA increases hippocampal <i>BDNF</i> expression and neurogenesis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 7","pages":"177-188"},"PeriodicalIF":2.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141361008","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}

{"title":"Heterogeneous distribution of mitochondria and succinate dehydrogenase activity in human airway smooth muscle cells","authors":"Sanjana Mahadev Bhat,&nbsp;Gary C. Sieck","doi":"10.1096/fba.2024-00047","DOIUrl":"https://doi.org/10.1096/fba.2024-00047","url":null,"abstract":"<p>Succinate dehydrogenase (SDH) is a key mitochondrial enzyme involved in the tricarboxylic acid cycle, where it facilitates the oxidation of succinate to fumarate, and is coupled to the reduction of ubiquinone in the electron transport chain as Complex II. Previously, we developed a confocal-based quantitative histochemical technique to determine the maximum velocity of the SDH reaction (SDH_max) in single cells and observed that SDH_max corresponds with mitochondrial volume density. In addition, mitochondrial volume and motility varied within different compartments of human airway smooth muscle (hASM) cells. Therefore, we hypothesize that the SDH activity varies relative to the intracellular mitochondrial volume within hASM cells. Using 3D confocal imaging of labeled mitochondria and a concentric shell method for analysis, we quantified mitochondrial volume density, mitochondrial complexity index, and SDH_max relative to the distance from the nuclear membrane. The mitochondria within individual hASM cells were more filamentous in the immediate perinuclear region and were more fragmented in the distal parts of the cell. Within each shell, SDH_max also corresponded to mitochondrial volume density, where both peaked in the perinuclear region and decreased in more distal parts of the cell. Additionally, when normalized to mitochondrial volume, SDH_max was lower in the perinuclear region when compared to the distal parts of the cell. In summary, our results demonstrate that SDH_max measures differences in SDH activity within different cellular compartments. Importantly, our data indicate that mitochondria within individual cells are morphologically heterogeneous, and their distribution varies substantially within different cellular compartments, with distinct functional properties.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 6","pages":"159-176"},"PeriodicalIF":2.7,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251512","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}

{"title":"The effects of oxidative stress and intracellular calcium on mitochondrial permeability transition pore formation in equine spermatozoa","authors":"Zamira Gibb,&nbsp;Robert J. Aitken,&nbsp;Alecia R. Sheridan,&nbsp;Brandan Holt,&nbsp;Stephanie Waugh,&nbsp;Aleona Swegen","doi":"10.1096/fba.2023-00051","DOIUrl":"10.1096/fba.2023-00051","url":null,"abstract":"<p>The in vitro storage of stallion spermatozoa for use in artificial insemination leads to oxidative stress and imbalances in calcium homeostasis that trigger the formation of the mitochondrial permeability transition pore (mPTP), resulting in premature cell death. However, little is understood about the dynamics and the role of mPTP formation in mammalian spermatozoa. Here, we identify an important role for mPTP in stallion sperm Ca²⁺ homeostasis. We show that stallion spermatozoa do not exhibit “classical” features of mPTP; specifically, they are resistant to cyclosporin A-mediated inhibition of mPTP formation, and they do not require exogenous Ca²⁺ to form the mPTP. However, chelation of endogenous Ca²⁺ prevented mPTP formation, indicating a role for intracellular Ca²⁺ in this process. Furthermore, our findings suggest that this cell type can mobilize intracellular Ca²⁺ stores to form the mPTP in response to low Ca²⁺ environments and that under oxidative stress conditions, mPTP formation preceded a measurable increase in intracellular Ca²⁺, and vice versa. Contrary to previous work that identified mitochondrial membrane potential (MMP) as a proxy for mPTP formation, here we show that a loss of MMP can occur independently of mPTP formation, and thus MMP is not an appropriate proxy for the detection of mPTP formation. In conclusion, the mPTP plays a crucial role in maintaining Ca²⁺ and reactive oxygen species homeostasis in stallion spermatozoa, serving as an important regulatory mechanism for normal sperm function, thereby contraindicating the in vitro pharmacological inhibition of mPTP formation to enhance sperm longevity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 6","pages":"143-158"},"PeriodicalIF":2.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141016951","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}

{"title":"Unraveling the ultrastructure and dynamics of autophagic vesicles: Insights from advanced imaging techniques","authors":"Ting Jiang,&nbsp;Chaoye Ma,&nbsp;Hao Chen","doi":"10.1096/fba.2024-00035","DOIUrl":"10.1096/fba.2024-00035","url":null,"abstract":"<p>Autophagy, an intracellular self-degradation process, is governed by a complex interplay of signaling pathways and interactions between proteins and organelles. Its fundamental purpose is to efficiently clear and recycle cellular components that are damaged or redundant. Central to this process are autophagic vesicles, specialized structures that encapsulate targeted cellular elements, playing a pivotal role in autophagy. Despite growing interest in the molecular components of autophagic machinery and their regulatory mechanisms, capturing the detailed ultrastructural dynamics of autophagosome formation continues to present significant challenges. However, recent advancements in microscopy, particularly in electron microscopy, have begun to illuminate the dynamic regulatory processes underpinning autophagy. This review endeavors to provide an exhaustive overview of contemporary research on the ultrastructure of autophagic processes. By synthesizing observations from diverse technological methodologies, this review seeks to deepen our understanding of the genesis of autophagic vesicles, their membrane origins, and the dynamic alterations that transpire during the autophagy process. The aim is to bridge gaps in current knowledge and foster a more comprehensive comprehension of this crucial cellular mechanism.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 7","pages":"189-199"},"PeriodicalIF":2.5,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022081","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}

{"title":"Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction-associated steatotic liver disease","authors":"Olufunto O. Badmus,&nbsp;Alexandre A. da Silva,&nbsp;Xuan Li,&nbsp;Lucy C. Taylor,&nbsp;Jennifer R. Greer,&nbsp;Andrew R. Wasson,&nbsp;Karis E. McGowan,&nbsp;Parth R. Patel,&nbsp;David E. Stec","doi":"10.1096/fba.2023-00139","DOIUrl":"10.1096/fba.2023-00139","url":null,"abstract":"<p>The leading cause of death among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is cardiovascular disease. A significant percentage of MASLD patients develop heart failure driven by functional and structural alterations in the heart. Previously, we observed cardiac dysfunction in hepatocyte-specific peroxisome proliferator-activated receptor alpha knockout (<i>Ppara</i>^HepKO), a mouse model that exhibits hepatic steatosis independent of obesity and insulin resistance. The goal of the present study was to determine mechanisms that underlie hepatic steatosis-induced cardiac dysfunction in <i>Ppara</i>^HepKO mice. Experiments were performed in 30-week-old <i>Ppara</i>^HepKO and littermate control mice fed regular chow. We observed decreased cardiomyocyte contractility (0.17 ± 0.02 vs. 0.24 ± 0.02 μm, <i>p</i> &lt; 0.05), increased cardiac triglyceride content (0.96 ± 0.13 vs. 0.68 ± 0.06 mM, <i>p</i> &lt; 0.05), collagen type 1 (4.65 ± 0.25 vs. 0.31 ± 0.01 AU, <i>p</i> &lt; 0.001), and collagen type 3 deposition (1.32 ± 0.46 vs. 0.05 ± 0.03 AU, <i>p</i> &lt; 0.05). These changes were associated with increased apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (30.9 ± 4.7 vs. 13.1 ± 0.8%, <i>p</i> &lt; 0.006) and western blots showing increased cleaved caspase-3 (0.27 ± 0.006 vs. 0.08 ± 0.01 AU, <i>p</i> &lt; 0.003) and pro-caspase-3 (5.4 ± 1.5 vs. 0.5 ± 0.3 AU, <i>p</i> &lt; 0.02), B-cell lymphoma protein 2-associated X (0.68 ± 0.07 vs. 0.04 ± 0.04 AU, <i>p</i> &lt; 0.001), and reduced B-cell lymphoma protein 2 (0.29 ± 0.01 vs. 1.47 ± 0.54 AU, <i>p</i> &lt; 0.05). We further observed elevated circulating natriuretic peptides and exercise intolerance in <i>Ppara</i>^HepKO mice when compared to controls. Our data demonstrated that lipotoxicity, and fibrosis underlie cardiac dysfunction in MASLD.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 5","pages":"131-142"},"PeriodicalIF":2.7,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140372197","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}

{"title":"FASEB BioAdvances announces changes in 2024","authors":"Loren E. Wold,&nbsp;Crislyn D'Souza-Schorey,&nbsp;Yung Hou Wong","doi":"10.1096/fba.2024-00043","DOIUrl":"10.1096/fba.2024-00043","url":null,"abstract":"&lt;p&gt;In 2019, The Federation of American Societies for Experimental Biology (FASEB) started publishing &lt;i&gt;FASEB BioAdvances&lt;/i&gt; as a fully open-access partner to its flagship &lt;i&gt;FASEB Journal&lt;/i&gt; for authors to publish their quality research spanning the breadth of the biological and biomedical sciences. Today, the journal publishes a variety of manuscript types, including original research, reviews, and perspectives on current issues in science and academia. The scope of &lt;i&gt;FASEB BioAdvances&lt;/i&gt; overlaps with &lt;i&gt;The FASEB Journal&lt;/i&gt;, and although its priority is also quality science, it puts less emphasis on perceived impact (e.g., is a sound science journal) and now also welcomes manuscript types that we believe will improve rigor and reproducibility, including replication studies or reports on negative (null) findings.&lt;/p&gt;&lt;p&gt;Drs. Crislyn D'Souza-Schorey and Yung Hou Wong have served as Editors-in-Chief since January 2022. During their tenure, they have focused their efforts on timely review and publication of cutting-edge science, cross-disciplinary science, and original research. Their efforts have repositioned the journal with a focus that serves it well into the future.&lt;/p&gt;&lt;p&gt;Recently, FASEB considered how to best grow published output in &lt;i&gt;FASEB BioAdvances&lt;/i&gt; without reducing quality or compromising on scientific integrity. FASEB's analysis also identified a need for a seamless process for authors transferring manuscripts from &lt;i&gt;The FASEB Journal&lt;/i&gt; to &lt;i&gt;FASEB BioAdvances&lt;/i&gt; in a way that further strengthens their partnership. In an effort to increase the value of &lt;i&gt;FASEB BioAdvances&lt;/i&gt; to its authors, to decrease the time to first decision, and to better align with the needs of the global author community served by FASEB, we are announcing a change in the editorial structure of the journal. Since February 2024, &lt;i&gt;FASEB BioAdvances&lt;/i&gt; is under the direction of Loren E. Wold, PhD, Editor-in-Chief of &lt;i&gt;The FASEB Journal&lt;/i&gt; who will work to strengthen both journals. Dr. Wold and team are working on enhancing manuscript transfer options for authors, adding a new dedicated Referral Editor to work between both journals to be a resource for authors, and a plan to introduce greater emphasis on the publication of thematic special collections in areas of considerable importance. &lt;i&gt;The FASEB Journal&lt;/i&gt; is fortunate to already have in place a team of over 200 dedicated and diverse researchers: a Senior Editor, a team of eight Associate Editors, and a Special Issues and Reviews Editor, an almost 100-member editorial board, and a 116-member early career researcher editorial board. The &lt;i&gt;FASEB BioAdvances&lt;/i&gt; Deputy Editor will continue to serve in that role and will join &lt;i&gt;The FASEB Journal&lt;/i&gt; editorial team. Associate Editors of &lt;i&gt;FASEB BioAdvances&lt;/i&gt; will continue to serve in their roles. Leveraging this new, broad, and expanded editorial team for both journals will be an important advantage for authors by ensuring rapid review, edi","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 4","pages":"103-104"},"PeriodicalIF":2.7,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140227217","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}

{"title":"The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer","authors":"Bo Ma,&nbsp;Lei Xiu,&nbsp;Lili Ding","doi":"10.1096/fba.2023-00083","DOIUrl":"10.1096/fba.2023-00083","url":null,"abstract":"<p>N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3′ untranslated regions (3′-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 4","pages":"105-117"},"PeriodicalIF":2.7,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140240296","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}

{"title":"Recent progresses in gut microbiome mediates obstructive sleep apnea-induced cardiovascular diseases","authors":"Xiaotong Zhang,&nbsp;Haifen Zhang,&nbsp;Shuai Li,&nbsp;Fan Fang,&nbsp;Yanran Yin,&nbsp;Qiang Wang","doi":"10.1096/fba.2023-00153","DOIUrl":"10.1096/fba.2023-00153","url":null,"abstract":"<p>Obstructive sleep apnea (OSA) is a multifactorial sleep disorder with a high prevalence in the general population. OSA is associated with an increased risk of developing cardiovascular diseases (CVDs), particularly hypertension, and is linked to worse outcomes. Although the correlation between OSA and CVDs is firmly established, the mechanisms are poorly understood. Continuous positive airway pressure is primary treatment for OSA reducing cardiovascular risk effectively, while is limited by inadequate compliance. Moreover, alternative treatments for cardiovascular complications in OSA are currently not available. Recently, there has been considerable attention on the significant correlation between gut microbiome and pathophysiological changes in OSA. Furthermore, gut microbiome has a significant impact on the cardiovascular complications that arise from OSA. Nevertheless, a detailed understanding of this association is lacking. This review examines recent advancements to clarify the link between the gut microbiome, OSA, and OSA-related CVDs, with a specific focus on hypertension, and also explores potential health advantages of adjuvant therapy that targets the gut microbiome in OSA.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 4","pages":"118-130"},"PeriodicalIF":2.7,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140078501","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}

{"title":"ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity","authors":"Jianjian Shi,&nbsp;Lei Wei","doi":"10.1096/fba.2024-00015","DOIUrl":"https://doi.org/10.1096/fba.2024-00015","url":null,"abstract":"<p>In this study, we investigated the roles of ROCK1 in regulating structural and functional features of caveolae located at the cell membrane of cardiomyocytes, adipocytes, and mouse embryonic fibroblasts (MEFs) as well as related physiopathological effects. Caveolae are small bulb-shaped cell membrane invaginations, and their roles have been associated with disease conditions. One of the unique features of caveolae is that they are physically linked to the actin cytoskeleton that is well known to be regulated by RhoA/ROCKs pathway. In cardiomyocytes, we observed that ROCK1 deficiency is coincident with an increased caveolar density, clusters, and caveolar proteins including caveolin-1 and -3. In the mouse cardiomyopathy model with transgenic overexpressing Gαq in myocardium, we demonstrated the reduced caveolar density at cell membrane and reduced caveolar protein contents. Interestingly, coexisting ROCK1 deficiency in cardiomyocytes can rescue these defects and preserve caveolar compartmentalization of β-adrenergic signaling molecules including β1-adrenergic receptor and type V/VI adenylyl cyclase. In cardiomyocytes and adipocytes, we detected that ROCK1 deficiency increased insulin signaling with increased insulin receptor activation in caveolae. In MEFs, we identified that ROCK1 deficiency increased caveolar and total levels of caveolin-1 and cell membrane repair ability after mechanical or chemical disruptions. Together, these results demonstrate that ROCK1 can regulate caveolae plasticity and multiple functions including compartmentalization of signaling molecules and cell membrane repair following membrane disruption by mechanical force and oxidative damage. These findings provide possible molecular insights into the beneficial effects of ROCK1 deletion/inhibition in cardiomyocytes, adipocytes, and MEFs under certain diseased conditions.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 3","pages":"85-102"},"PeriodicalIF":2.7,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053252","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}

{"title":"Loss of chaperone-mediated autophagy does not alter age-related bone loss in male mice","authors":"James A. Hendrixson,&nbsp;Alicen James,&nbsp;Nisreen S. Akel,&nbsp;Dominique J. Laster,&nbsp;Julie A. Crawford,&nbsp;Stuart B. Berryhill,&nbsp;Melda Onal","doi":"10.1096/fba.2023-00133","DOIUrl":"https://doi.org/10.1096/fba.2023-00133","url":null,"abstract":"<p>Chaperone-mediated autophagy (CMA) is a lysosome-dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age-associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age-associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS-32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age-related bone loss, we hypothesized that declining CMA contributes to the age-associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA-deficient mice and controls up to 24 months of age and examined age-associated changes in bone mass and architecture. We showed that lack of CMA did not alter age-associated decline in bone mineral density as measured by dual x-ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA-deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age-related bone loss.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 3","pages":"73-84"},"PeriodicalIF":2.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053256","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}