Search results for "proteolysis"

Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.

2016

The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that CD99 undergoes ectodomain shedding by the metalloprotease meprin β and subsequent intramembrane proteolysis by γ-secretase. The cleavage site in CD99 was identified by mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly to the unique cleavage specificity of meprin β with a strong preference for aspartate residues and suggests coevolution of protease and substrate. We hypothesized that limited CD99 cleavage by meprin β would alter cellular transendothelial migratio…

The Metalloprotease Meprin β Is an Alternative β-Secretase of APP

2017

The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The latter event was discussed to be rather neuroprotective, whereas the ectodomain shedding of APP by meprin β reminiscent to BACE-1 is in line with the amyloid h…

Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis

2019

CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…

2020

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that…

The N-terminal domain of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for its acclimative proteolysis.

2000

AbstractVariations in the amount of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for regulation of the uptake of light into photosystem II. An endogenous proteolytic system was found to be involved in the degradation of LHCII in response to elevated light intensities and the proteolysis was shown to be under tight regulation [Yang, D.-H. et al. (1998) Plant Physiol. 118, 827–834]. In this study, the substrate specificity and recognition site towards the protease were examined using reconstituted wild-type and mutant recombinant LHCII. The results show that the LHCII apoprotein and the monomeric form of the holoprotein are targeted for proteolysis while t…

F1-ATPase from Micrococcus sp. ATCC 398. Purification by Ion-Exchange Chromatography and Further Characterization. (Auto)proteolysis and Dissociative…

1977

The preparation of highly purified F1-ATPase from Micrococcus sp. ATCC 398 by application of DEAE-Sepharose CL-6B chromatography as final step is described. This enzyme consists of five subunits of different molecular weight: alpha (65000), beta (55000),gamma (35000), delta (20000), and epsilon (17000). Disc electrophoresis on 5% polyacrylamide gels removes the epsilon-polypeptide yielding an active ATPase complex with four different subunits: alpha, beta, gamma, delta. Additionally, by variation of the ionic strength delta can (partly) removed allowing the isolation by disc electrophoresis of an active ATPase complex which consists only of three different subunits alpha, beta, and gamma. I…

Salivary composition in obese vs normal-weight subjects: towards a role in postprandial lipid metabolism?

2015

In the pathophysiological context of obesity, oral exposure to dietary fat can modulate lipid digestion and absorption but underlying in-mouth mechanisms have not been clearly identified. Therefore we tested the hypothesis that salivary components related to dietary fat sensitivity would differ according to BMI and postprandial lipid metabolism in young men. Saliva was collected from 9 normal-weight (BMI=22.3±0.5 kg/m2) and 9 non-morbid obese (BMI=31.7±0.3 kg/m2) men before a 8 h-postprandial metabolic exploration test involving the consumption of a 40 g fat-meal, in which obese subjects revealed a delayed postprandial lipid metabolism. Nine salivary characteristics (flow, protein content, …

Variability of human saliva composition: possible relationships with fat perception and liking

2012

International audience; Saliva is the medium that bathes the taste receptors in the oral cavity and in which aroma and taste compounds are released when food is eaten. Moreover saliva contains enzymes and molecules that can interact with food. To date, little research has been devoted to the intra- and inter-individual variabilities of these components and their inter-relationships. The first aim of this work was to study intra- and inter-individual variabilities over time in the composition of molecules likely to interact with food in the mouth, with particular focus on molecules that might interact with fat. The second aim was to try to relate this composition to a liking for fat and its …

Salivary Composition Is Associated with Liking and Usual Nutrient Intake

2015

Salivary flow and composition have an impact on flavor perception. However, very few studies have explored the relationship between saliva, individual liking and usual dietary intake. The aim of our study was to evaluate the association of salivary flow and composition with both a liking for fat, saltiness and sweetness and the usual nutrient intake in an adult French population. Liking for fat, saltiness, and sweetness were inferred from liking scores obtained during hedonic tests on 32 food products among 282 French adults participating in the Nutrinet- Santé Study. Before assessing liking, resting saliva was collected. Standard biochemical analyses were performed to assess specific compo…

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity

2019

AbstractThe association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30–35 or BMI>35) of o…