Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"Expression, purification and characterization of a dual function α-dioxygenase/peroxidase from Mycolicibacterium smegmatis.","authors":"Teresa Rotolo, Anna Kaye, Lauren Fahrenkrog, Kate Flynn, Elisabeth C Ford, Barry S Selinsky","doi":"10.1016/j.bbalip.2024.159587","DOIUrl":"10.1016/j.bbalip.2024.159587","url":null,"abstract":"<p><p>An open reading frame from the actinobacterium Mycolicibacterium smegmatis annotated as a Prostaglandin H Synthase (PGHS) was expressed with an N-terminal (his)₆ tag and purified to homogeneity. The enzyme has a monomeric molecular weight of 68.3 kD and exists as a dimer in the presence of nonionic detergent. The enzyme uses saturated and unsaturated fatty acids as substrates and catalyzes two reactions: the addition of molecular oxygen alpha to the carboxylate group to form the 2-hydroperoxy fatty acid, followed by reduction to the 2-hydroxy fatty acid. The initial reduction reaction does not require a source of electrons, but electrons must be provided from an appropriate donor such as epinephrine for the reduction reaction to go to completion. Minor reaction products one carbon atom shorter than the original fatty acid substrate are also observed; These most likely arise from the spontaneous decarboxylation of the 2-hydroperoxy fatty acid product to form an aldehyde. This dual function dioxygenase/peroxidase is unusual among the lipid dioxygenases and may represent a bacterial precursor to mammalian PGHS.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159587"},"PeriodicalIF":3.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862772","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":"Effect of glucose selenol on hepatic lipid metabolism disorder induced by heavy metal cadmium in male rats.","authors":"Xinyi Yang, Jinzhou Huang, Juan Wang, Huimin Sun, JinJin Li, Shunfeng Li, Yun-E Tang, Zhi Wang, Qisheng Song","doi":"10.1016/j.bbalip.2024.159589","DOIUrl":"10.1016/j.bbalip.2024.159589","url":null,"abstract":"<p><p>This study used 24 male rats to determine the protective effects of a new selenium molecule (glucose selenol) on cadmium (Cd) induced hepatic toxicity. The rats were randomly divided into four groups: control group, Cd group, Cd + 0.15 Se group, and Cd + 0.4 Se group. The results showed that glucose selenol supplementation alleviated the adverse impact of Cd on lipid metabolism, including decreased serum triacylglycerol and cholesterol levels. Transcriptome analysis revealed that, compared to the control group, Cd changed the expression of 1379 genes - discernibly affecting lipid metabolism pathways. Proteomic analysis primarily indicated alterations in lipid metabolism-related pathways. In conclusion, glucose selenol restored lipid metabolism disorders induced by Cd, thus rescuing hepatic damage. This integrated analysis identified the influence of glucose selenol on Cd-induced hepatic toxicity and provided its potential application prospects in alleviating the impact of heavy metal pollution, such as Cd, on human health.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159589"},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823780","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":"Effect of N-glycosylation on secretion, degradation and lipoprotein distribution of human serum amyloid A4.","authors":"Toru Takarada, Rikako Fujinaka, Masaki Shimada, Masakazu Fukuda, Toshiyuki Yamada, Masafumi Tanaka","doi":"10.1016/j.bbalip.2024.159588","DOIUrl":"10.1016/j.bbalip.2024.159588","url":null,"abstract":"<p><p>Serum amyloid A (SAA) is a family of apolipoproteins predominantly synthesized and secreted by the liver. Human SAA4 is constitutively expressed and contains an N-glycosylation site that is not present in other SAA subtypes. SAA4 proteins are not fully glycosylated, resulting in the presence of both glycosylated and non-glycosylated forms in human plasma. The efficiency of N-glycosylation in SAA4 is known to be influenced by some reasons such as genetic polymorphism and metabolic disorders. However, the specific role of N-glycosylation in SAA4 remains largely unexplored. This study aimed to investigate how N-glycosylation affects the secretion, degradation, and lipoprotein distribution of SAA4. Initially, we designed and constructed an SAA4 plasmid vector to compare with the expression pattern of endogenous SAA4. The exogenous SAA4 was partially N-glycosylated, analogous to endogenous SAA4 in human hepatocellular carcinoma cells. Subsequently, we created a non-glycosylated mutant by replacing asparagine 76 with glutamine. Immunoblotting assays showed that the disruption of N-glycans did not affect the secretion and degradation of SAA4. Furthermore, we analyzed the lipoprotein profiles of SAA4 in the conditioned medium derived from transfected cells. The results revealed that non-glycosylated mutant SAA4 exhibited a distinct lipoprotein distribution compared to wild-type SAA4. Our findings suggest that N-glycosylation may be a key regulator of the distribution of SAA4 in lipoproteins, shedding light on the previously unknown physiological activities of human SAA4.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159588"},"PeriodicalIF":3.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821725","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":"Origin and evolution of yeast carotenoid pathways.","authors":"Gerhard Sandmann","doi":"10.1016/j.bbalip.2024.159586","DOIUrl":"10.1016/j.bbalip.2024.159586","url":null,"abstract":"<p><p>Carotenoid pathways exist in nature in all domains. Comparison of the genes involved and their distribution allowed the elucidation of the origin and evolution of carotenoid biosynthesis from an early common ancestor of prokaryotes to Bacteria and Archaea. From the latter domain, carotenogenic genes are inherited by fungi as the only phylum of Eukarya. Carotenoid biosynthesis in the algal-plant lineage emerged independently by endosymbiotic gene transfer from an engulfed carotenogenic cyanobacterium. The early set of carotenogenic genes included crtB of phytoene synthase, the desaturase gene crtI, and the lycopene cyclase gene crtYcd for the synthesis of β-carotene. This carotenoid is further metabolised either to zeaxanthin and retinal due to the presence of crtZ and ccd or elongated to a C₅₀ carotenoids by the crtEb gene product. The diversified pathways, especially in bacteria and fungi, result from gene modifications altering the substrate and product specificities of the corresponding enzymes or from the acquisition of novel genes. This was highlighted in more detail for the carotenoid pathways in the red yeasts of Basidiomycota leading to torularhodin, 2'-plectaniaxanthin, and astaxanthin.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159586"},"PeriodicalIF":3.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817105","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":"Single-cell transcriptomic analysis and luteolin treatment reveal three adipogenic genes, including Aspn, Htra1 and Efemp1.","authors":"Tao Tao, Yanting Xu, Cheng-Hui Zhang, Xian Zhang, Juan Chen, Jian Liu","doi":"10.1016/j.bbalip.2024.159585","DOIUrl":"10.1016/j.bbalip.2024.159585","url":null,"abstract":"<p><p>A comparative transcriptomic analysis in adipose stem and progenitor cells (ASPCs) between obese and lean mice might facilitate the identification of novel adipogenic genes. Here, we compare transcriptomic differences in the ASPCs of subcutaneous adipose tissue (SAT) between the mice fed on a high-fat-diet (HFD) and the chow diet (CD)-fed mice by analyzing three independent single-cell RNA sequencing datasets. Six differential genes, including three up-regulated genes Aspn, Rrbp1, Fbln2 and three down-regulated genes Htra1, Plpp3, Efemp1, are identified and confirmed in HFD-fed mice. Further, the expression of these genes is found to be significantly diminished in the differentiated 3T3-L1 cells. Treatment with luteolin, a dietary flavonoid known to inhibit 3T3-L1 adipogenesis, reverses the decreased expression of Aspn, Htra1 and Efemp1. Furthermore, knockdown of Aspn, Htra1 and Efemp1 significantly facilitates 3T3-L1 adipogenesis. Together, these genes not only are differential in ASPCs between obese and lean mice, but also are the adipogenic inhibitory genes that can be up-regulated by luteolin treatment.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159585"},"PeriodicalIF":3.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812134","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":"The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner.","authors":"Youn-Kyung Kim, Elena Giordano, Ulrich Hammerling, Dhruv Champaneri, Johannes von Lintig, M Mahmood Hussain, Loredana Quadro","doi":"10.1016/j.bbalip.2024.159584","DOIUrl":"10.1016/j.bbalip.2024.159584","url":null,"abstract":"<p><p>Vitamin A is an essential nutrient crucial to ensuring proper mammalian embryonic development. β-Carotene is the most prevalent form of vitamin A in food that, when transferred in its intact form from mother to the developing tissues, can serve as an in situ source of retinoic acid, the active form of vitamin A. We have previously provided evidence that the maternal-fetal transfer of β-carotene across the placenta is mediated by lipoproteins and that β-carotene itself regulates placenta lipoprotein biogenesis by means of its derivatives β-apo-10'-carotenoids and retinoic acid. These metabolites exert antagonistic transcriptional activity on placental microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), two key players of lipoprotein biosynthesis. Here, we analyzed the time-dependency of this regulation over the course of 24 h upon a single maternal administration of β-carotene. We also tested the hypothesis that the transcriptional repressor intestine-specific homeobox (ISX) plays a role in the regulation of Mttp in placenta. We observed that ISX is expressed in placenta of mouse dams and is regulated by β-carotene availability. Furthermore, we demonstrated that the absence of Isx disrupts the β-carotene-mediated regulation of placental MTP. We also showed that this mechanism is organ-specific, as it was not observed in enterocytes of the intestine, a major place of Isx expression. Therefore, we identified ISX as a \"master\" regulator of a placental β-carotene-dependent transcriptional regulatory cascade that fine-tunes the flux of provitamin A carotenoid towards the developing fetus.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159584"},"PeriodicalIF":3.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790970","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":"PLAAT5 as an N-acyltransferase responsible for the generation of anti-inflammatory N-acylethanolamines in testis","authors":"Mohammad Mamun Sikder ,&nbsp;Sumire Sasaki ,&nbsp;Yoshimi Miki ,&nbsp;Yuki Nagasaki ,&nbsp;Ken-ichi Ohta ,&nbsp;Zahir Hussain ,&nbsp;Hiroyuki Saiga ,&nbsp;Mari Ohmura-Hoshino ,&nbsp;Katsuaki Hoshino ,&nbsp;Masaki Ueno ,&nbsp;Miki Okada-Iwabu ,&nbsp;Makoto Murakami ,&nbsp;Natsuo Ueda ,&nbsp;Toru Uyama","doi":"10.1016/j.bbalip.2024.159583","DOIUrl":"10.1016/j.bbalip.2024.159583","url":null,"abstract":"<div><div><em>N</em>-Acylethanolamines (NAEs) are a class of lipid mediators that exhibit anti-inflammatory and appetite-suppressive activities. Among them, palmitoylethanolamide (PEA) and arachidonoylethanolamide (AEA) bind to peroxisomal proliferator-activated receptor (PPAR) α and cannabinoid receptor CB1, respectively. <em>N</em>-Acyl-phosphatidylethanolamine (NAPE) as a precursor of NAEs is biosynthesized from membrane phospholipids by <em>N</em>-acyltransferases, which consist of group IVE cytosolic phospholipase A₂ε (cPLA₂ε) and PLAAT (phospholipase A and acyltransferase) family enzymes. While cPLA₂ε is responsible for the production of NAEs not only in specific tissues, including muscle, skin, and the stomach, but also under pathological conditions, such as psoriasis and brain ischemia, the involvement of the PLAAT family <em>in vivo</em> remains unclear. Considering the specific expression of PLAAT5 in testes, we investigated the potential role of PLAAT5 in the formation of NAEs in testes using PLAAT5-deficient (<em>Plaat5</em>^{<em>−/−</em>}) mice. High-performance liquid chromatography coupled with tandem mass spectrometry showed that PLAAT5 deficiency decreased the total level of NAEs by 61 %, with PEA and AEA being reduced by 64 % and 87 %, respectively. Following a treatment with cadmium chloride, an environmental toxin that induces testicular inflammation, the expression of inflammatory genes (<em>Il6</em>, <em>Tnf</em>, and <em>Nos2</em>) in testes was markedly higher in <em>Plaat5</em>^{<em>−/−</em>} mice than in <em>Plaat5</em>^<em>+/+</em> mice, and their expression was attenuated by the administration of PEA and AEA. Furthermore, these anti-inflammatory effects were canceled by a co-treatment with the antagonists of PPARα or CB1. These results suggest that PLAAT5 is responsible for the biosynthesis of anti-inflammatory NAEs in testes.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159583"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725331","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":"Dysregulated mitochondrial fission and neurodegeneration proteomic signature in ACSF3-deficient cells","authors":"Khaled Alatibi ,&nbsp;Kathrin Sumser ,&nbsp;Maria Elpida Christopoulou ,&nbsp;Martin J. Hug ,&nbsp;Sara Tucci","doi":"10.1016/j.bbalip.2024.159582","DOIUrl":"10.1016/j.bbalip.2024.159582","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159582"},"PeriodicalIF":3.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706392","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":"Role of USF1 in activating CYBA transcription and influencing NADPH-ROS-mediated oxidative stress and lipid accumulation in non-alcoholic fatty liver disease","authors":"Shaohua Zhuang ,&nbsp;Jinjin Fu ,&nbsp;Liwei Wu ,&nbsp;Xuanfu Xu ,&nbsp;Chuanyong Guo","doi":"10.1016/j.bbalip.2024.159581","DOIUrl":"10.1016/j.bbalip.2024.159581","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) progression is relevant to oxidative stress, while NADPH oxidase can produce ROS. This study explored how the upstream stimulatory factor 1 (USF1) regulates cytochrome <em>b</em>-245 alpha chain (CYBA) expression through the NADPH-ROS pathway and its impact on oxidative stress and lipid accumulation in NAFLD. Bioinformatics analysis identified CYBA as a gene with altered expression in NAFLD. Mouse and cell models of NAFLD were established through high-fat diet (HFD) and palmitic acid (PA) treatment respectively. CYBA and USF1 expression was modulated using RNA interference, and their effects on NAFLD progression were then examined. ChIP and dual-luciferase reporter assays were performed to confirm the transcriptional regulation of CYBA by USF1. Elevated CYBA expression was observed in NAFLD. Reduced NADPH oxidase activity, oxidative stress, lipid accumulation, and inflammation were observed in NAFLD models after knocking down CYBA. USF1 was found to bind to the CYBA promoter and activate its transcription. Similar effects as CYBA knockdown on NAFLD were achieved by knocking down USF1. The protective impacts of USF1 silencing on NAFLD were reversed by overexpressing CYBA. In summary, this study demonstrates that USF1 mediates the transcriptional activation of CYBA, increasing NADPH-ROS-derived oxidative stress and lipid accumulation in NAFLD.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159581"},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692594","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":"RBM15 promotes lipogenesis and malignancy in gastric cancer by regulating N6-Methyladenosine modification of ACLY mRNA in an IGF2BP2-dependent manner","authors":"Xianlei Cai ,&nbsp;Xueying Li ,&nbsp;Miaozun Zhang ,&nbsp;Zhebin Dong ,&nbsp;Yihui Weng ,&nbsp;Weiming Yu","doi":"10.1016/j.bbalip.2024.159580","DOIUrl":"10.1016/j.bbalip.2024.159580","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) and lipid metabolism reprogramming play pivotal roles in cancer development. Nevertheless, the precise functions of m⁶A methyltransferase RNA Binding Motif Protein 15 (RBM15) and its interactions with ATP Citrate Lyase (ACLY) in gastric cancer (GC) have not been fully elucidated. In this study, we comprehensively investigate the biological roles and potential mechanisms of RBM15 and ACLY in GC. We employed a combination of fundamental experiments and bioinformatics analyses to unravel the enigmatic roles of RBM15 and ACLY. The expression of RBM15 was evaluated. The biological roles of RBM15 in GC cells were investigated through <em>in vitro</em> and <em>in vivo</em> studies. ACLY was selected as the candidate target of RBM15. Subsequently, to decipher the underlying mechanisms of the RBM15/ACLY axis, we conducted a series of experiments including methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, and RNA immunoprecipitation qPCR. We observed a conspicuous upregulation of RBM15 in GC, and its heightened expression was associated with an unfavorable prognosis. Functionally, RBM15 fostered the proliferation and invasiveness of GC cells both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, ACLY emerged as the downstream target of RBM15 and it was validated as an oncogene in GC cells. RBM15 mediated the activation of ACLY by regulating m6A modification in an IGF2BP2-dependent manner, thereby driving lipogenesis and exacerbating the malignant characteristics in GC. The activation of ACLY, facilitated by RBM15/IGF2BP2-mediated m6A modification, drives lipogenesis and promotes the progression of GC.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159580"},"PeriodicalIF":3.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643835","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}