Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: implications for exosome stability and biology

Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically diverse species and can be used by parasites to alter the properties of the host environment. Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be diverse based on the physiology and environmental niche of different organisms. Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we term exosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those from the nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs, which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on diversity in the molecular properties of EVs that enable them to function in cross-species communication

The role of lipocalin-2 in age-related macular degeneration (AMD)

Lipocalins are a family of secreted adipokines which play important roles in various biological processes. Lipocalin-2 (LCN-2) has been shown to be involved in acute and chronic inflammation. This particular protein is critical in the pathogenesis of several diseases including cancer, diabetes, obesity, and multiple sclerosis. Herein, we discuss the general molecular basis for the involvement of LCN-2 in acute infections and chronic disease progression and also ascertain the probable role of LCN-2 in ocular diseases, particularly in age-related macular degeneration (AMD). We elaborate on the signaling cascades which trigger LCN-2 upregulation in AMD and suggest therapeutic strategies for targeting such pathways

βA3/A1-crystallin is required for proper astrocyte template formation and vascular remodeling in the retina

Nuc1 is a spontaneous rat mutant resulting from a mutation in the Cryba1 gene, coding for βA3/A1-crystallin. Our earlier studies with Nuc1 provided novel evidence that astrocytes, which express βA3/A1-crystallin, have a pivotal role in retinal remodeling. The role of astrocytes in the retina is only beginning to be explored. One of the limitations in the field is the lack of appropriate animal models to better investigate the function of astrocytes in retinal health and disease. We have now established transgenic mice that overexpress the Nuc1 mutant form of Cryba1, specifically in astrocytes. Astrocytes in wild type mice show normal compact stellate structure, producing a honeycomb-like network. In contrast, in transgenics over-expressing the mutant (Nuc1) Cryba1 in astrocytes, bundle-like structures with abnormal patterns and morphology were observed. In the nerve fiber layer of the transgenic mice, an additional layer of astrocytes adjacent to the vitreous is evident. This abnormal organization of astrocytes affects both the superficial and deep retinal vascular density and remodeling. Fluorescein angiography showed increased venous dilation and tortuosity of branches in the transgenic retina, as compared to wild type. Moreover, there appear to be fewer interactions between astrocytes and endothelial cells in the transgenic retina than in normal mouse retina. Further, astrocytes overexpressing the mutant βA3/A1-crystallin migrate into the vitreous, and ensheath the hyaloid artery, in a manner similar to that seen in the Nuc1 rat. Together, these data demonstrate that developmental abnormalities of astrocytes can affect the normal remodeling process of both fetal and retinal vessels of the eye and that βA3/A1-crystallin is essential for normal astrocyte function in the retina

Anti-aging effect and gene expression profiling of dung beetle glycosaminoglycan in aged rats

Abstract Background This study aimed to evaluate the anti-aging effect of a newly prepared insect-derived compound, dung beetle glycosaminoglycan (GAG), given intraperitoneally to old SD rats as part of their diet for 1 month. Insect GAG administration was found to be related to a reduction in oxidative damage, hepato-cellular biomarker levels, protein carbonyl content, and malondialdehyde concentration. The anti-aging-related molecular genetic mechanisms of dung beetle GAG are not yet fully elucidated. Results Catharsius molossus (a type of dung beetle) GAG (CaG) possessed anti-aging activities; it reduced the serum level of creatinine kinase, had aortic vasorelaxant activities and cardioprotective actions, and maintained a normal glucose level in treated rats. Microarray analysis was performed with a rat 30 K cDNA clone set array to identify the gene-expression profiles of 14-month-old SD rats treated with dung beetle glycosaminoglycan 5 mg/kg (CaG5) over a 1-month period, which was done to investigate its anti-aging effect as compared to that of either Bombus ignitus (a type of bumblebee) queen GAG 5 mg/kg (IQG5) or chondroitin sulfate 10 mg/kg. CaG5 and IQG5 had marked anti-inflammatory effects, bringing about inhibition of free fatty acid, uric acid, sGPT, IL-1 beta, and CK values. In addition, anticoagulant and antithrombotic effects were seen: the concentration of factor 1 (fibrinogen) was increased in CaG- treated rat plasma. The CaG5-treated rat group, compared to the control, displayed upregulation of 131 genes, including lipocalin 2 (Lbp) and a serine peptidase inhibitor, Kaszal type3 (Spink3), and 64 downregulated genes, including lysyl oxidase (Lox), serine dehydratase (sds), and retinol saturase (Retsat). Conclusion Our data suggest that dung beetle glycosaminoglycan may be a helpful treatment for aged rats, which indicates its potential as a therapeutic biomaterial for aging