Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Monocyte and macrophage profiles in patients with inherited long-chain fatty acid oxidation disorders","authors":"Sanne G.S. Verberk ,&nbsp;Nico Hahn ,&nbsp;Daan Heister ,&nbsp;Jorien Haverkamp ,&nbsp;Khya S. Snelder ,&nbsp;Kyra E. de Goede ,&nbsp;Friederieke S. Gorki ,&nbsp;Jerome J.A. Hendriks ,&nbsp;Riekelt H. Houtkooper ,&nbsp;Gepke Visser ,&nbsp;Barbara Sjouke ,&nbsp;Mirjam Langeveld ,&nbsp;Jan Van den Bossche","doi":"10.1016/j.bbadis.2024.167524","DOIUrl":"10.1016/j.bbadis.2024.167524","url":null,"abstract":"<div><div>Patients with inherited disorders of the long-chain fatty acid oxidation (lcFAO) machinery present with a heterogeneous profile of disease manifestations and aggravation of symptoms is often triggered by inflammatory activation. Monocytes and macrophages are innate immune cells that play a major role in the onset and resolution of inflammation. These cells undergo metabolic rewiring upon activation including the regulation of the FAO rate. The rewiring of FAO and the effect of lcFAO disorders (lcFAOD) on human monocyte and macrophage phenotype and function remain largely unknown. Here, we performed extensive phenotyping of circulating monocytes and analyzed plasma cytokine levels in 11 lcFAOD patients and 11 matched control subjects. In patients with lcFAOD, we observed induced plasma levels of the inflammatory cytokines IL-1β and IL-6, and enhanced CD206 and CD62L surface marker expression in circulating monocyte subsets. To mimic the most common lcFAOD very-long-chain acyl-CoA dehydrogenase disorder (VLCADD), we used siRNA-mediated knockdown of the <em>ACADVL</em> gene (encoding VLCAD) in macrophages derived from healthy volunteers. Hereby, we found that siVLCAD affected IL-4-induced alternative macrophage activation while leaving LPS responses and cellular metabolism intact. In the same line, monocyte-derived macrophages from lcFAOD patients had elevated levels of the IL-4-induced alternative macrophage markers CD206 and CD200R. Still, they did not show major metabolic defects or changes in the LPS-induced inflammatory response. Our results indicate that monocytes and macrophages from lcFAOD patients present no major inflammatory or metabolic differences and show that IL-4-induced surface markers are intertwined with lcFAO in human macrophages.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167524"},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303287","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}

{"title":"Pathophysiological significance of the p.E31G variant in RAC1 responsible for a neurodevelopmental disorder with microcephaly","authors":"Masashi Nishikawa ,&nbsp;Shin Hayashi ,&nbsp;Atsushi Nakayama ,&nbsp;Yosuke Nishio ,&nbsp;Anna Shiraki ,&nbsp;Hidenori Ito ,&nbsp;Kouichi Maruyama ,&nbsp;Yukako Muramatsu ,&nbsp;Tomoo Ogi ,&nbsp;Seiji Mizuno ,&nbsp;Koh-ichi Nagata","doi":"10.1016/j.bbadis.2024.167520","DOIUrl":"10.1016/j.bbadis.2024.167520","url":null,"abstract":"<div><div><em>RAC1</em> encodes a Rho family small GTPase that regulates actin cytoskeletal reorganization and intracellular signaling pathways. Pathogenic <em>RAC1</em> variants lead to a neurodevelopmental disorder with diverse phenotypic manifestations, including abnormalities in brain size and facial dysmorphism. However, the underlying pathophysiological mechanisms have yet to be elucidated. Here, we present the case of a school-aged male who exhibited global developmental delay, intellectual disability, and acquired microcephaly. Through whole exome sequencing, we identified a novel de novo variant in <em>RAC1</em>, (NM_006908.5): c.92 A &gt; G,p.(E31G). We then examined the pathophysiological significance of the p.E31G variant by focusing on brain development. Biochemical analyses revealed that the recombinant RAC1-E31G had no discernible impact on the intrinsic GDP/GTP exchange activity. However, it exhibited a slight inhibitory effect on GTP hydrolysis. Conversely, it demonstrated a typical response to both a guanine-nucleotide exchange factor and a GTPase-activating protein. In transient expression analyses using COS7 cells, RAC1-E31G exhibited minimal interaction with the downstream effector PAK1, even in its GTP-bound state. Additionally, overexpression of RAC1-E31G was observed to exert a weak inhibitory effect on the differentiation of primary cultured hippocampal neurons. Moreover, in vivo studies employing in utero electroporation revealed that acute expression of RAC1-E31G resulted in impairments in axonal elongation and dendritic arborization in the young adult stage. These findings suggest that the p.E31G variant functions as a dominant-negative version in the PAK1-mediated signaling pathway and is responsible for the clinical features observed in the patient under investigation, namely microcephaly and intellectual disability.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167520"},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303288","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}

{"title":"Role of Elavl-like RNA-binding protein in retinal development and signal transduction.","authors":"Huxitaer Wutikeli ,&nbsp;Yao Yu ,&nbsp;Tianlu Zhang ,&nbsp;Jingjing Cao ,&nbsp;Scott Nawy ,&nbsp;Yin Shen","doi":"10.1016/j.bbadis.2024.167518","DOIUrl":"10.1016/j.bbadis.2024.167518","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) play central roles in post-transcriptional gene regulation. However, the function of RBP in retinal progenitor cell differentiation and synaptic signal transmission are largely unexplored. Previously we have shown that Elavl2 regulates amacrine cell (AC) differentiation during retinogenesis, by directly binding to Nr4a2 and Barhl2. Elavl2 is expressed in early neuronal progenitors to mature neurons, and Elavl4 expression begins slightly later, during cortical neuron development as a paralog. Here, Retinal-specific Elavl2 and Elavl4 double knockout mice were made to further explore the role of Elavl2 and Elavl4 in retinal development and signal transduction. We disclose that Elavl4 binds to Satb1 to regulate Neurod1, then promoting retinal progenitor and amacrine cells differentiation. We were also surprised to find that Elavl2 interacted with GABA_B receptors at the RNA and protein levels. In conclusion, Elavl2 and Elavl4 regulate amacrine cells differentiation through different pathways, leading to decreased scotopic vision. Our findings reveal the roles of Elavl2 and Elavl4 in retinal amacrine cells differentiation in modulating visual functions.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167518"},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303289","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}

{"title":"Postnatally overfed mice display cardiac function alteration following myocardial infarction","authors":"Marie Josse ,&nbsp;Eve Rigal ,&nbsp;Nathalie Rosenblatt-Velin ,&nbsp;Bertrand Collin ,&nbsp;Geoffrey Dogon ,&nbsp;Luc Rochette ,&nbsp;Marianne Zeller ,&nbsp;Catherine Vergely","doi":"10.1016/j.bbadis.2024.167516","DOIUrl":"10.1016/j.bbadis.2024.167516","url":null,"abstract":"<div><h3>Background</h3><p>Cardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction.</p></div><div><h3>Methods</h3><p>C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection.</p></div><div><h3>Findings</h3><p>At 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups.</p></div><div><h3>Interpretation</h3><p>After MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 1","pages":"Article 167516"},"PeriodicalIF":4.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0925443924005106/pdfft?md5=ca76416df6a5a5ff2b4adda24515d813&pid=1-s2.0-S0925443924005106-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273691","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}

{"title":"Mitochondria: new actor in cell-to-cell communication","authors":"Violaine Vandenhooft ,&nbsp;Florine Habets ,&nbsp;Aurélie Christian ,&nbsp;Luca Scorrano ,&nbsp;Ingrid Struman ,&nbsp;Stéphanie Herkenne","doi":"10.1016/j.bbadis.2024.167400","DOIUrl":"10.1016/j.bbadis.2024.167400","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167400"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142237314","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}

{"title":"Targeting mitophagy to maximize the immunostimulatory effects of radiation therapy in ER+ breast cancer","authors":"Emma Guilbaud ,&nbsp;Ai Sato ,&nbsp;Takahiro Yamazaki ,&nbsp;Lorenzo Galluzzi","doi":"10.1016/j.bbadis.2024.167381","DOIUrl":"10.1016/j.bbadis.2024.167381","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167381"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238433","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}

{"title":"Mitochondrial rheostat that predisposes to cancer","authors":"Aleksandra Filipovska","doi":"10.1016/j.bbadis.2024.167361","DOIUrl":"10.1016/j.bbadis.2024.167361","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167361"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238590","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}

{"title":"Exploration of the role of mitochondria in reactive oxygen species generation under moderate hypoxia at the hippocampal CA3 area","authors":"João L. Alves ,&nbsp;Marta S. Sousa ,&nbsp;Rosa M. Quinta-Ferreira ,&nbsp;Patrícia Reis ,&nbsp;M. Emília Quinta-Ferreira ,&nbsp;Carlos M. Matias","doi":"10.1016/j.bbadis.2024.167402","DOIUrl":"10.1016/j.bbadis.2024.167402","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167402"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238636","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}

{"title":"Molecular mechanisms of mitochondrial stress responses","authors":"Aleksandra Trifunovic","doi":"10.1016/j.bbadis.2024.167370","DOIUrl":"10.1016/j.bbadis.2024.167370","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167370"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238642","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}

{"title":"AIF-CHCHD4 dependent metabolic plasticity in pediatric cancer","authors":"Hong Toan Lai ,&nbsp;Daniela Pedroso ,&nbsp;Maria Eugenia Marques da Costa ,&nbsp;Romain Fernandes ,&nbsp;Antonin Marchais ,&nbsp;Nathalie Gaspar ,&nbsp;Birgit Geoerger ,&nbsp;Catherine Brenner","doi":"10.1016/j.bbadis.2024.167371","DOIUrl":"10.1016/j.bbadis.2024.167371","url":null,"abstract":"","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1870 8","pages":"Article 167371"},"PeriodicalIF":4.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238643","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}