Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells

Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A₂-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation.     

Resistance to pathogens in terpene down-regulated orange fruits inversely correlates with the accumulation of D-limonene in peel oil glands

Volatile organic compounds (VOCs) are secondary metabolites acting as a language for the communication of plants with the environment. In orange fruits, the monoterpene D-limonene accumulates at very high levels in oil glands from the peel. Drastic down-regulation of D-limonene synthase gene expression in the peel of transgenic oranges harboring a D-limonene synthase transgene in antisense (AS) configuration altered the monoterpene profile in oil glands, mainly resulting in reduced accumulation of D-limonene. This led to fruit resistance against Penicillium digitatum (Pd), Xanthomonas citri subsp. citri (Xcc) and other specialized pathogens. Here, we analyze resistance to pathogens in independent AS and empty vector (EV) lines, which have low, medium or high D-limonene concentrations and show that the level of resistance is inversely related to the accumulation of D-limonene in orange peels, thus explaining the need of high D-limonene accumulation in mature oranges in nature for the efficient attraction of specialized microorganism frugivores.     

Low metabolic rates in primitive hunters and weaver spiders

The rates of oxygen consumption and carbon dioxide release of primitive hunters and weaver spiders, the Chilean Recluse spider Loxosceles laeta Nicolet (Araneae: Sicariidae) and the Chilean Tiger spider Scytodes globula Nicolet (Araneae: Scytodidae), are analyzed, and their relationship with body mass is studied. The results are compared with the metabolic data available for other spiders. A low metabolic rate is found both for these two species and other primitive hunters and weavers, such as spiders of the families Dysderidae and Plectreuridae. The metabolic rate of this group is lower than in nonprimitive spiders, such as the orb weavers (Araneae: Araneidae). The results reject the proposition of a general relationship for metabolic rate for all land arthropods (related to body mass) and agree with the hypothesis that metabolic rates are affected not only by sex, reproductive and developmental status, but also by ecology and life style, recognizing here, at least in the araneomorph spiders, a group having low metabolism, comprising the primitive hunters and weaver spiders, and another group comprising the higher metabolic rate web building spiders (e.g. orb weavers).     

Restoration of CPEB4 prevents muscle stem cell senescence during aging

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骨钙素对能量代谢调节的研究进展

研究表明,骨钙素(osteocalcin)是由骨骼中成熟的成骨细胞合成并分泌的一种非胶原蛋白质,在骨骼的合成和重建过程中起着重要作用。近年来研究显示,骨骼亦可作为一种分泌器官,通过分泌骨钙素,作用于胰腺、脂肪、睾丸等器官,调节能量代谢、雄性生殖能力。此外,临床研究表明,骨钙素与糖尿病、心血管疾病等也有着密切的联系。因此,本文一方面概述了骨钙素的基本特征,另一方面着重介绍了骨钙素在调节能量代谢等方面的研究进展,以便为治疗糖尿病等代谢性疾病提供新的治疗靶点。     

The induction of antibiotic synthesis in Saccharopolyspora erythraea and Streptomyces hygroscopicus by growth rate decrease is accompanied by a down-regulation of protein synthesis rate

Abstract The relationship between antibiotic production and culture growth rate in Saccharopolyspora erythraea and Streptomyces hygroscopicus was manipulated by changing the growth-limiting substrate. Carbon- and nitrogen-limited cultures were studied and antibiotic synthesis was obtained in both cases in Saccharopolyspora erythraea cultures and in nitrogen-limited Streptomyces hygroscopicus cultures. In all cultures where antibiotic was detected, onset of antibiotic production coincided with the minimal protein synthesis rate. Further investigation in Saccharopolyspora erythraea cultures indicated that this corresponded to minimum ratio of charged to uncharged tRNA, i.e. when uncharged tRNA accumulated. This latter phenomenon was investigated in the presence of a protein synthesis inhibitor.     

ALBUMIN CAN REVERSE THE RELEASE OF POTASSIUM FROM HUMAN ERYTHROCYTES TREATED WITH THE NON-IONIC DETERGENT,BRIJ 58

Exchange of erythrocyte intracellular (i/c) K⁺for extracellular (e/c) Na⁺in human erythrocytes treated with sub-CMC concentrations of the non-ionic detergent Brij 58 can be stopped by reincubation in serum or albumin containing solutions. The progressive equilibration of the K⁺contents of detergent-treated human erythrocytes with the incubation medium was reversed by an albumin-mediated withdrawal of detergent molecules from the cell. Re-establishment of near normal [K⁺] in terms of K⁺/kg water proceeds in two ways: (i) a metabolism-dependent net accumulation of K⁺ions; and (ii) a metabolism-independent shrinkage of erythrocytes, this being the more significant factor.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Identification of a four-gene metabolic signature predicting overall survival for hepatocellular carcinoma

While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas—Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC.