Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine

Urinary exosomes have been proposed as potential diagnostic tools. TNF superfamily cytokines and receptors may be present in exosomes and are expressed by proximal tubular cells. We have now studied the expression of selected TNF superfamily proteins in exosome-like vesicles from cultured human proximal tubular cells and human urine and have identified additional proteins in these vesicles by LC-MS/MS proteomics. Human proximal tubular cells constitutively released exosome-like vesicles that did not contain the TNF superfamily cytokines TRAIL or TWEAK. However, exosome-like vesicles contained osteoprotegerin (OPG), a TNF receptor superfamily protein, as assessed by Western blot, ELISA or selected reaction monitoring by nLC-(QQQ)MS/MS. Twenty-one additional proteins were identified in tubular cell exosomelike vesicles, including one (vitamin D binding protein) that had not been previously reported in exosome-like vesicles. Twelve were extracellular matrix proteins, including the basement membrane proteins type IV collagen, nidogen-1, agrin and fibulin-1. Urine from chronic kidney disease patients contained a higher amount of exosomal protein and exosomal OPG than urine from healthy volunteers. Specifically OPG was increased in autosomal dominant polycystic kidney disease urinary exosome-like vesicles and expressed by cystic epithelium in vivo. In conclusion, OPG is present in exosome-like vesicles secreted by proximal tubular epithelial cells and isolated from Chronic Kidney Disease urine.This work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDINREN RD06/0016, RD12/0021, PI11/01854, PI10/00072 PI09/ 00641 and PS09/00447); Comunidad de Madrid (Fibroteam S2010/BMD-2321, S2010/BMD-2378); Sociedad Española de NefrologÍa; European Network (HEALTH F2-2008-200647); DIALOK European project LSHB-CT-2007-036644; Fundacion Lilly and IRSIN/FRIAT to JE; Programa Intensificación Actividad Investigadora (ISCIII/ Agencia Laín-Entralgo/CM) to AO; Instituto de Salud Carlos III (FIS PI11/01401, CP09/00229); and Fundación Conchita Rábago de Jiménez DÍaz to GAL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits

BACKGROUND: Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. RESULTS: Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. CONCLUSIONS: These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-015-0056-1) contains supplementary material, which is available to authorized users

Enzyme production from food wastes using a biorefinery concept

According to Food and Agricultural Organization (FAO), one-third of food produced globally for human consumption (nearly 1.3 billion tonnes) is lost along the food supply chain. In many countries food waste is currently landfilled or incinerated together with other combustible municipal wastes for possible recovery of energy. However, these two options are facing more and more economic and environmental stresses. Due to its organic- and nutrient-rich nature, theoretically food waste can be converted to valuable products (e.g. bio-products such as methane, hydrogen, ethanol, enzymes, organic acids, chemicals and fuels) through various fermentation processes. Such conversion of food waste is potentially more profitable than its conversion to animal feed or transportation fuel. Food waste valorisation has therefore gained interest, with value added bio-products such as methane, hydrogen, ethanol, enzymes, organic acids, chemicals, and fuels. Therefore, the aim of this review is to provide information on the food waste situation with emphasis on Asia–Pacific countries and the state of the art food waste processing technologies to produce enzymes

Chemical evidence for the origin of the cold water belt along the northeastern coast of Hokkaido

In the southwestern Okhotsk Sea, the cold water belt (CWB) is frequently observed on satellite images offshore of the Soya Warm Current flowing along the northeastern coast of Hokkaido, Japan, during summertime. It has been speculated that the CWB is upwelling cold water that originates from either subsurface water of the Japan Sea off Sakhalin or bottom water of the Okhotsk Sea. Hydrographic and chemical observations (nutrients, humic-type fluorescence intensity, and iron) were conducted in the northern Japan Sea and southwestern Okhotsk Sea in early summer 2011 to clarify the origin of the CWB. Temperature-salinity relationships, vertical distributions of chemical components, profiles of chemical components against density, and the (NO3 + NO2)/PO4 relationship confirm that water in the CWB predominantly originates from Japan Sea subsurface water