Biochimica et biophysica acta. Molecular basis of disease最新文献_第5页

Cancer stem cells: Masters of all traits 癌症干细胞：掌握所有特征

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-23 DOI: 10.1016/j.bbadis.2024.167549

Lionel Y.W. Leck , Yomna S. Abd El-Aziz , Kelly J. McKelvey , Kyung Chan Park , Sumit Sahni , Darius J.R. Lane , Jan Skoda , Patric J. Jansson

{"title":"Cancer stem cells: Masters of all traits","authors":"Lionel Y.W. Leck , Yomna S. Abd El-Aziz , Kelly J. McKelvey , Kyung Chan Park , Sumit Sahni , Darius J.R. Lane , Jan Skoda , Patric J. Jansson","doi":"10.1016/j.bbadis.2024.167549","DOIUrl":"10.1016/j.bbadis.2024.167549","url":null,"abstract":"<div><div>Cancer is a heterogeneous disease, which contributes to its rapid progression and therapeutic failure. Besides interpatient tumor heterogeneity, tumors within a single patient can present with a heterogeneous mix of genetically and phenotypically distinct subclones. These unique subclones can significantly impact the traits of cancer. With the plasticity that intratumoral heterogeneity provides, cancers can easily adapt to changes in their microenvironment and therapeutic exposure. Indeed, tumor cells dynamically shift between a more differentiated, rapidly proliferating state with limited tumorigenic potential and a cancer stem cell (CSC)-like state that resembles undifferentiated cellular precursors and is associated with high tumorigenicity. In this context, CSCs are functionally located at the apex of the tumor hierarchy, contributing to the initiation, maintenance, and progression of tumors, as they also represent the subpopulation of tumor cells most resistant to conventional anti-cancer therapies. Although the CSC model is well established, it is constantly evolving and being reshaped by advancing knowledge on the roles of CSCs in different cancer types. Here, we review the current evidence of how CSCs play a pivotal role in providing the many traits of aggressive tumors while simultaneously evading immunosurveillance and anti-cancer therapy in several cancer types. We discuss the key traits and characteristics of CSCs to provide updated insights into CSC biology and highlight its implications for therapeutic development and improved treatment of aggressive cancers.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167549"},"PeriodicalIF":4.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514561","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

Hyperglycaemia induces diet-dependent defects of the left-right axis by lowering intracellular pH 高血糖通过降低细胞内 pH 值诱发饮食依赖性左右轴缺陷。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-21 DOI: 10.1016/j.bbadis.2024.167550

Ryohei Matsuoka , Keiko Kitajima , Takenobu Nii , Zhaonan Zou , Kaori Tanaka , Kunihiko Joo , Yasuyuki Ohkawa , Shouichi Ohga , Chikara Meno

{"title":"Hyperglycaemia induces diet-dependent defects of the left-right axis by lowering intracellular pH","authors":"Ryohei Matsuoka , Keiko Kitajima , Takenobu Nii , Zhaonan Zou , Kaori Tanaka , Kunihiko Joo , Yasuyuki Ohkawa , Shouichi Ohga , Chikara Meno","doi":"10.1016/j.bbadis.2024.167550","DOIUrl":"10.1016/j.bbadis.2024.167550","url":null,"abstract":"<div><div>Pregestational diabetes is a risk factor for congenital anomalies, including heterotaxy syndrome, a rare birth defect characterized by the abnormal arrangement of organs relative to the left-right (L-R) body axis. To provide insight into the underlying mechanism by which diabetes induces heterotaxy, we here analyzed the L-R axis of mouse embryos of diabetic dams. Various <em>Pitx2</em> expression patterns indicative of disruption of L-R axis formation were apparent in such embryos. Expression of <em>Nodal</em> at the node, which triggers a <em>Nodal</em>-<em>Pitx2</em> expression cascade in lateral plate mesoderm, showed marked regression associated with L-R axis malformation. This regression was similar to that apparent in <em>Wnt3a</em><sup>−/−</sup> embryos, and canonical Wnt signalling was indeed found to be downregulated in embryos of diabetic dams. RNA sequencing revealed dysregulation of glycolysis in embryos of diabetic dams, and high glucose lowered intracellular pH in the primitive streak, leading to the suppression of Wnt signalling and the regression of <em>Nodal</em> expression. Of note, maternal vitamin A intake increased the incidence of L-R axis defects in embryos of diabetic dams, with dysregulation of retinoic acid metabolism being apparent in these embryos and in <em>Wnt3a</em><sup>−/−</sup> embryos. Our results shed light on the mechanisms underlying embryopathies associated with maternal diabetes and suggest the importance of diet for prevention of heterotaxy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167550"},"PeriodicalIF":4.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514564","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

Increased NPM1 inhibit ferroptosis and aggravate renal fibrosis via Nrf2 pathway in chronic kidney disease 慢性肾脏病患者体内 NPM1 的增加会通过 Nrf2 途径抑制铁蛋白沉积并加重肾脏纤维化。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-20 DOI: 10.1016/j.bbadis.2024.167551

Wenjing Fu , Mingyu Zhang , Yilin Meng , Jingyu Wang , Li Sun

{"title":"Increased NPM1 inhibit ferroptosis and aggravate renal fibrosis via Nrf2 pathway in chronic kidney disease","authors":"Wenjing Fu , Mingyu Zhang , Yilin Meng , Jingyu Wang , Li Sun","doi":"10.1016/j.bbadis.2024.167551","DOIUrl":"10.1016/j.bbadis.2024.167551","url":null,"abstract":"<div><div>Recent findings underscore the significance of ferroptosis, an innovative iron-dependent mode of cell death, in the etiology and progression of chronic kidney disease (CKD). Nucleophosmin 1 (NPM1), a nucleolar protein, contributes to fibrogenesis and modulates cellular functions and mortality. Initial investigations utilized bioinformatics techniques to pinpoint genes with altered expression in CKD and to forecast the potential links between NPM1, ferroptosis, and renal fibrosis. Increased NPM1 expression was verified in the renal tissues of CKD patients. Experimental models of renal fibrosis in both animals and cells were then used for further study. The suppression of NPM1 led to an augmentation in iron metabolism and lipid peroxidation processes integral to ferroptosis, contributing to the mitigation of renal fibrosis. In contrast, an elevation in NPM1 expression had the opposite effect. This modulation may be interconnected with the nuclear factor erythroid 2–related factor 2 pathway. Moreover, the application of the ferroptosis inhibitor, Fer-1, not only obstructed ferroptosis but also diminished NPM1 expression, which, in turn, contributed to the alleviation of renal fibrosis. Thus, our findings suggest that in CKD the NPM1 level increased and led to decreased ferroptosis and aggravated renal fibrosis via an Nrf2 pathway. Ferroptosis inhibitor can alleviate renal fibrosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167551"},"PeriodicalIF":4.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mitostasis in age-associated neurodegeneration 与年龄相关的神经变性中的有丝分裂。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-20 DOI: 10.1016/j.bbadis.2024.167547

Mrutyunjaya Panda , Maria Markaki , Nektarios Tavernarakis

{"title":"Mitostasis in age-associated neurodegeneration","authors":"Mrutyunjaya Panda , Maria Markaki , Nektarios Tavernarakis","doi":"10.1016/j.bbadis.2024.167547","DOIUrl":"10.1016/j.bbadis.2024.167547","url":null,"abstract":"<div><div>Mitochondria are essential organelles that play crucial roles in various metabolic and signalling pathways. Proper neuronal function is highly dependent on the health of these organelles. Of note, the intricate structure of neurons poses a critical challenge for the transport and distribution of mitochondria to specific energy-intensive domains, such as synapses and dendritic appendages. When faced with chronic metabolic challenges and bioenergetic deficits, neurons undergo degeneration. Unsurprisingly, disruption of mitostasis, the process of maintaining cellular mitochondrial content and function within physiological limits, has been implicated in the pathogenesis of several age-associated neurodegenerative disorders. Indeed, compromised integrity and metabolic activity of mitochondria is a principal hallmark of neurodegeneration. In this review, we survey recent findings elucidating the role of impaired mitochondrial homeostasis and metabolism in the onset and progression of age-related neurodegenerative disorders. We also discuss the importance of neuronal mitostasis, with an emphasis on the major mitochondrial homeostatic and metabolic pathways that contribute to the proper functioning of neurons. A comprehensive delineation of these pathways is crucial for the development of early diagnostic and intervention approaches against neurodegeneration.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167547"},"PeriodicalIF":4.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514562","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

Conditional Pten inactivation in pituitary results in sex-specific prolactinoma formation 垂体中的条件性 Pten 失活导致催乳素瘤的形成具有性别特异性。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-18 DOI: 10.1016/j.bbadis.2024.167543

Álvaro Flores-Martínez , Víctor Darío Ramos-Herrero , Alexia Barroso , Alicia Moreno , Miguel E. G-García , Eva Venegas-Moreno , Elena Dios , Juan Pedro Martínez-Barberá , Raúl M. Luque , Alfonso Soto-Moreno , David A. Cano

{"title":"Conditional Pten inactivation in pituitary results in sex-specific prolactinoma formation","authors":"Álvaro Flores-Martínez , Víctor Darío Ramos-Herrero , Alexia Barroso , Alicia Moreno , Miguel E. G-García , Eva Venegas-Moreno , Elena Dios , Juan Pedro Martínez-Barberá , Raúl M. Luque , Alfonso Soto-Moreno , David A. Cano","doi":"10.1016/j.bbadis.2024.167543","DOIUrl":"10.1016/j.bbadis.2024.167543","url":null,"abstract":"<div><div>Pituitary tumors, including prolactinomas, present significant clinical challenges that require a deeper understanding of their molecular roots for improved diagnostics and therapies. Here, we investigate the role of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K) pathway in pituitary tumorigenesis using a mouse model. Conditional knockout of <em>Pten</em> in all pituitary cell lineages resulted in prolactinoma formation exclusively in female mice, demonstrating the critical role of PTEN in pituitary homeostasis. While <em>Pten</em> inactivation induced Akt activation in all pituitary cells, only prolactin-producing cells exhibited tumorigenic changes, suggesting specific cell-type effects. Histological and molecular analyses of prolactinomas revealed similarities with human pituitary tumors, such as decreased vascularization and cell adhesion proteins and increased accumulation of cell cycle proteins. Notably, prolactinomas displayed diminished levels of phosphorylated extracellular signal-regulated kinase (ERK), implicating downregulation of ERK in tumorigenesis. Finally, we analyzed PTEN/PI3K activation in a collection of human pituitary tumors. Overall, our study delineates the intricate interplay between the PTEN and ERK signaling pathways, providing insights into sex-specific mechanisms of pituitary tumorigenesis and potential therapeutic strategies for prolactinomas.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167543"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482865","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

Severe dynein dysfunction in cholinergic neurons exacerbates ALS-like phenotypes in a new mouse model 在一种新的小鼠模型中，胆碱能神经元中严重的动力蛋白功能障碍会加剧类似渐冻人症的表型。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-18 DOI: 10.1016/j.bbadis.2024.167540

Fabio A. Simoes , Eleni Christoforidou , Raphaelle Cassel , Luc Dupuis , Majid Hafezparast

{"title":"Severe dynein dysfunction in cholinergic neurons exacerbates ALS-like phenotypes in a new mouse model","authors":"Fabio A. Simoes , Eleni Christoforidou , Raphaelle Cassel , Luc Dupuis , Majid Hafezparast","doi":"10.1016/j.bbadis.2024.167540","DOIUrl":"10.1016/j.bbadis.2024.167540","url":null,"abstract":"<div><div>Cytoplasmic dynein 1, a motor protein essential for retrograde axonal transport, is increasingly implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In this study, we developed a novel mouse model that combines the <em>Legs at odd angles</em> (<em>Loa</em>, F580Y) point mutation in the dynein heavy chain with a cholinergic neuron-specific knockout of the dynein heavy chain. This model, for the first time, allows us to investigate the impact of <em>Loa</em> allele exclusivity in these neurons into adulthood. Our findings reveal that this selective increase in dynein dysfunction exacerbated the phenotypes observed in heterozygous <em>Loa</em> mice including pre-wean survival, reduced body weight and grip strength. Additionally, it induced ALS-like pathology in neuromuscular junctions (NMJs) not seen in heterozygous <em>Loa</em> mice. Notably, we also found a previously unobserved significant increase in neurons displaying TDP-43 puncta in both <em>Loa</em> mutants, suggesting early TDP-43 mislocalisation – a hallmark of ALS. The novel model also exhibited a concurrent rise in p62 puncta that did not co-localise with TDP-43, indicating broader impairments in autophagic clearance mechanisms. Overall, this new model underscores the fact that dynein impairment alone can induce ALS-like pathology and provides a valuable platform to further explore the role of dynein in ALS.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167540"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Fatty acid β-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models 脑线粒体中的脂肪酸β氧化：从小鼠、大鼠和果蝇大脑、缺血和衰老模型的高分辨率呼吸测量中获得的启示。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-17 DOI: 10.1016/j.bbadis.2024.167544

Luiza H.D. Cardoso , Cristiane Cecatto , Melita Ozola , Stanislava Korzh , Liga Zvejniece , Baiba Gukalova , Carolina Doerrier , Maija Dambrova , Marina Makrecka-Kuka , Erich Gnaiger , Edgars Liepinsh

{"title":"Fatty acid β-oxidation in brain mitochondria: Insights from high-resolution respirometry in mouse, rat and Drosophila brain, ischemia and aging models","authors":"Luiza H.D. Cardoso , Cristiane Cecatto , Melita Ozola , Stanislava Korzh , Liga Zvejniece , Baiba Gukalova , Carolina Doerrier , Maija Dambrova , Marina Makrecka-Kuka , Erich Gnaiger , Edgars Liepinsh","doi":"10.1016/j.bbadis.2024.167544","DOIUrl":"10.1016/j.bbadis.2024.167544","url":null,"abstract":"<div><div>Glucose is the main energy source of the brain, yet recent studies demonstrate that fatty acid oxidation (FAO) plays a relevant role in the pathogenesis of central nervous system disorders. We evaluated FAO in brain mitochondria under physiological conditions, in the aging brain, and after stroke. Using high-resolution respirometry we compared medium-chain (MC, octanoylcarnitine) and long-chain (LC, palmitoylcarnitine) acylcarnitines as substrates of β-oxidation in the brain. The protocols developed avoid FAO overestimation by malate-linked anaplerotic activity in brain mitochondria. The capacity of FA oxidative phosphorylation (F-OXPHOS) with palmitoylcarnitine was up to 4 times higher than respiration with octanoylcarnitine. The optimal concentration of palmitoylcarnitine was 10 μM which corresponds to the total concentration of LC acylcarnitines in the brain. Maximal respiration with octanoylcarnitine was reached at 20 μM, however, this concentration exceeds MC acylcarnitine concentrations in the brain 15 times. F-OXPHOS capacity was highest in mouse cerebellum, intermediate in cortex, prefrontal cortex, and hypothalamus, and hardly detectable in hippocampus. F-OXPHOS capacity was 2-fold lower and concentrations of LC acylcarnitines were 2-fold higher in brain of aged rats. A similar trend was observed in the rat model of endothelin-1-induced stroke, but reduction of OXPHOS capacity was not limited to FAO. In conclusion, although FAO is not a dominant pathway in brain bioenergetics, it deserves specific attention in studies of brain metabolism.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167544"},"PeriodicalIF":4.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

PFKP inhibition protects against pathological cardiac hypertrophy by regulating protein synthesis 抑制 PFKP 可通过调节蛋白质合成防止病理性心肌肥厚

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-15 DOI: 10.1016/j.bbadis.2024.167542

Xiao-Yu Wu , Shi Peng , Xin-Tao Li , Song-Wen Chen , Yong Wei , Yu-Tong Ye , Chang-Zuan Zhou , Zi-Kan Zhong , Long-Zhe Gao , Chen-Yang Jin , De-Ping Kong , Shao-Wen Liu , Gen-Qing Zhou

{"title":"PFKP inhibition protects against pathological cardiac hypertrophy by regulating protein synthesis","authors":"Xiao-Yu Wu , Shi Peng , Xin-Tao Li , Song-Wen Chen , Yong Wei , Yu-Tong Ye , Chang-Zuan Zhou , Zi-Kan Zhong , Long-Zhe Gao , Chen-Yang Jin , De-Ping Kong , Shao-Wen Liu , Gen-Qing Zhou","doi":"10.1016/j.bbadis.2024.167542","DOIUrl":"10.1016/j.bbadis.2024.167542","url":null,"abstract":"<div><div>Metabolic reprogramming precedes most alterations during pathological cardiac hypertrophy and heart failure (HF). Recent studies have revealed that Phosphofructokinase, platelet (PFKP) has a wealth of metabolic and non-metabolic functions. In this study, we explored the role of PFKP in cardiac hypertrophic growth and HF. The expression level of PFKP was elevated both in pathological cardiac remodeling mouse model challenged by transverse aortic constriction (TAC) surgery and in the neonatal rat cardiomyocytes (NRCMs) stimulated by phenylephrine (PE). In global PFKP knockout (PFKP-KO) mice, cardiac hypertrophy was ameliorated under TAC surgery, while overexpression of PFKP by intravenous injection of adeno-associated virus 9 (AAV9) under the cardiac troponin T (cTnT) promoter worsened myocardial hypertrophy and fibrosis. In NRCMs, small interfering RNA (SiRNA) knockdown or adenovirus (Adv) overexpression of PFKP was employed and the intervention of PFKP showed a similar phenotype. Mechanistically, immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (IP-MS/MS) analysis was used to identify the interacting proteins of PFKP. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) was identified as the downstream target of PFKP. In the PE-stimulated NRCM hypertrophy model and mouse TAC model, knocking down EIF2S2 after PFKP overexpression reduced the synthesis of new proteins and alleviated the hypertrophy phenotype. Our findings illuminate that PFKP participates in pathological cardiac hypertrophy partly by regulating protein synthesis through EIF2S2, which provides a new clue for the involvement of metabolic intermediates in signal transduction.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167542"},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA) 脑铁积聚性神经变性 MPAN 亚型（NBIA）患者成纤维细胞中的代谢变化。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-15 DOI: 10.1016/j.bbadis.2024.167541

Agata Wydrych , Barbara Pakuła , Patrycja Jakubek-Olszewska , Justyna Janikiewicz , Aneta M. Dobosz , Agnieszka Cudna , Marcel Rydzewski , Karolina Pierzynowska , Lidia Gaffke , Zuzanna Cyske , Estera Rintz , Iwona Kurkowska-Jastrzębska , Maciej Cwyl , Paolo Pinton , Grzegorz Węgrzyn , Werner J.H. Koopman , Agnieszka Dobrzyń , Marta Skowrońska , Magdalena Lebiedzińska-Arciszewska , Mariusz R. Wieckowski

{"title":"Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA)","authors":"Agata Wydrych , Barbara Pakuła , Patrycja Jakubek-Olszewska , Justyna Janikiewicz , Aneta M. Dobosz , Agnieszka Cudna , Marcel Rydzewski , Karolina Pierzynowska , Lidia Gaffke , Zuzanna Cyske , Estera Rintz , Iwona Kurkowska-Jastrzębska , Maciej Cwyl , Paolo Pinton , Grzegorz Węgrzyn , Werner J.H. Koopman , Agnieszka Dobrzyń , Marta Skowrońska , Magdalena Lebiedzińska-Arciszewska , Mariusz R. Wieckowski","doi":"10.1016/j.bbadis.2024.167541","DOIUrl":"10.1016/j.bbadis.2024.167541","url":null,"abstract":"<div><div>Mutations in the following genes: <em>PANK2</em>, <em>PLA2G6</em>, <em>C19orf12</em>, <em>WDR45</em>, <em>CP</em>, <em>FA2H</em>, <em>ATP13A2</em>, <em>FTL</em>, <em>DCAF17</em>, and <em>CoASY</em> are associated with the development of different subtypes of inherited rare disease Neurodegeneration with Brain Iron Accumulation (NBIA). Additionally, recently described mutations in <em>FTH1</em>, <em>AP4M1</em>, <em>REPS1</em>, <em>SCP2</em>, <em>CRAT</em> and <em>GTPBP2</em> affecting iron and lipid metabolism also are thought to be involved in NBIA development. Four main subtypes, pantothenate kinase-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), mitochondrial membrane protein-associated neurodegeneration (MPAN) and beta-propeller protein-associated neurodegeneration (BPAN), are responsible for up to 82 % of all NBIA cases. Here we studied fibroblasts from 11 patients with pathogenic mutations in <em>C19orf12</em>, and demonstrate various cellular aberrations. Differences between fibroblasts from healthy individuals and MPAN patients were potentiated when cells were grown under oxidative phosphorylation (OXPHOS) promoting condition suggesting an impaired metabolic flexibility. The extent of some of the cellular aberrations quantitatively correlated with disease severity, suggesting their involvement in the NBIA pathomechanism.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167541"},"PeriodicalIF":4.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Nuclear localization of APLF facilitates breast cancer metastasis APLF 的核定位促进了乳腺癌的转移。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-09 DOI: 10.1016/j.bbadis.2024.167537

Debparna Nandy , Mayur Balkrishna Shirude , Archana S. , Anjali Devarajan , Ananda Mukherjee , Debasree Dutta

{"title":"Nuclear localization of APLF facilitates breast cancer metastasis","authors":"Debparna Nandy , Mayur Balkrishna Shirude , Archana S. , Anjali Devarajan , Ananda Mukherjee , Debasree Dutta","doi":"10.1016/j.bbadis.2024.167537","DOIUrl":"10.1016/j.bbadis.2024.167537","url":null,"abstract":"<div><div>Most breast cancer deaths result from metastases. We previously reported that DNA repair factor and histone chaperone Aprataxin PNK-like Factor (APLF) is involved in EMT-associated metastasis of triple negative breast cancer (TNBC) cells. However, non-metastatic cells also expressed APLF, the implications of which in disease advancement remain uncertain. Here, we demonstrate that the metastatic prognosis of breast cancer cells may be determined by the cellular localization of APLF. Using TNBC patient samples and cell lines, we discovered that APLF was localized in the nucleus and cytoplasm, whereas other subtypes of breast cancer had cytosolic or perinuclear localization. To investigate metastatic properties in vitro and in vivo, we modeled APLF differential localization by stably producing APLF-tagged nuclear localization signal (NLS) in the luminal subtype MCF7 cells in the absence of putative APLF NLS. Nuclear APLF in non-metastatic MCF7 cells demonstrated pronounced migration, invasion and metastatic potential. We obtained the mechanistic insight from molecular studies that PARP1 could facilitate the transport of APLF from the cytosol to the nucleus, assisting in the metastasis of TNBC cells linked with EMT. Inhibition of PARP1 enzymatic activity with olaparib abrogated the nuclear expression of APLF with loss in expression of genes associated with EMT. Thus, our findings reveal that cellular localization of APLF may predict the risk of breast cancer to metastasize and hence could be exploited to determine the disease progression. We anticipate that the inhibition of cytosolic PARP1-APLF interaction may potentially aid in the prevention of breast cancer metastasis in TNBC patients.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167537"},"PeriodicalIF":4.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395896","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}

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