Search results for "Protein Precursor"
showing 10 items of 169 documents
Progastrin Represses the Alternative Activation of Human Macrophages and Modulates Their Influence on Colon Cancer Epithelial Cells
2014
Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influe…
Circadian System Functionality, Hippocampal Oxidative Stress, and Spatial Memory in the APPswe/PS1dE9 Transgenic Model of Alzheimer Disease: Effects …
2012
Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mou…
Up‐regulation of the α‐secretase ADAM10 by retinoic acid receptors and acitretin
2009
Late-onset Alzheimer's disease is often connected with nutritional misbalance, such as enhanced cholesterol intake, deficiency in polyunsaturated fatty acids, or hypovitaminosis. The alpha-secretase ADAM10 has been found to be regulated by retinoic acid, the bioreactive metabolite of vitamin A. Here we show that retinoids induce gene expression of ADAM10 and alpha-secretase activity by nonpermissive retinoid acid receptor/retinoid X receptor (RAR/RXR) heterodimers, whereby alpha- and beta-isotypes of RAR play a major role. However, ligands of other RXR binding partners, such as the vitamin D receptor, do not stimulate alpha-secretase activity. On the basis of these findings, we examined the…
Factors associated with plasma antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide concentrations in acute heart failure
2020
Background: Plasma amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 levels are positively associated with a higher risk of adverse clinical outcomes in acute heart failure. As a proxy of congestion, antigen carbohydrate 125 has also been proposed as a right-sided heart failure marker. Thus, we aimed to determine in this population the main factors – including echocardiographic right-sided heart failure parameters – associated with antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide. Methods and results: We prospectively included 2949 patients admitted with acute heart failure. Amino-terminal pro-B-type natriuretic peptide and antigen carbohy…
Presepsin and Midregional Proadrenomedullin in Pediatric Oncologic Patients with Febrile Neutropenia
2020
Abstract Objective In this study, we investigated the roles of presepsin (PSP) and midregional proadrenomedullin (mr-proADM) in children with febrile neutropenia (FN) due to chemotherapy. Methods We assessed 36 FN episodes in 26 children. Patients were classified into bacteremia (B) and fever of unknown origin (FUO) groups. We evaluated PSP and mr-proADM at admission (T0), after 24/48 h (T1), and after 5 days (T2). Results PSP and mr-proADM levels were elevated at T0 and significantly decreased at T2. mr-proADM levels did not significantly differ between the B and FUO groups. PSP levels significantly differed between the B and FUO groups only at T1. Both PSP and mr-proADM levels at T0 were …
Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength.
2013
Type I fibrillar collagen is the most abundant protein in the human body, crucial for the formation and strength of bones, skin, and tendon. Proteolytic enzymes are essential for initiation of the assembly of collagen fibrils by cleaving off the propeptides. We report that Mep1a −/− and Mep1b −/− mice revealed lower amounts of mature collagen I compared with WT mice and exhibited significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength. While exploring the mechanism of this phenotype, we found that cleavage of full-length human procollagen I heterotrimers by either meprin α or meprin β led to the generation of mature collagen molecules that s…
(19)F NMR screening of unrelated antimicrobial peptides shows that membrane interactions are largely governed by lipids.
2014
AbstractMany amphiphilic antimicrobial peptides permeabilize bacterial membranes via successive steps of binding, re-alignment and/or oligomerization. Here, we have systematically compared the lipid interactions of two structurally unrelated peptides: the cyclic β-pleated gramicidin S (GS), and the α-helical PGLa. 19F NMR was used to screen their molecular alignment in various model membranes over a wide range of temperatures. Both peptides were found to respond to the phase state and composition of these different samples in a similar way. In phosphatidylcholines, both peptides first bind to the bilayer surface. Above a certain threshold concentration they can re-align and immerse more dee…
Cholesterol-Like Effects of Selective Cyclooxygenase Inhibitors and Fibrates on Cellular Membranes and Amyloid-β Production
2007
Strong evidence suggests a mechanistic link between cholesterol metabolism and the formation of amyloid-beta peptides, the principal constituents of senile plaques found in the brains of patients with Alzheimer's disease. Here, we show that several fibrates and diaryl heterocycle cyclooxygenase inhibitors, among them the commonly used drugs fenofibrate and celecoxib, exhibit effects similar to those of cholesterol on cellular membranes and amyloid precursor protein (APP) processing. These drugs have the same effects on membrane rigidity as cholesterol, monitored here by an increase in fluorescence anisotropy. The effect of the drugs on cellular membranes was also reflected in the inhibitory…
Measurement of cerebral ABCC1 transport activity in wild-type and APP/PS1-21 mice with positron emission tomography
2020
Previous data suggest a possible link between multidrug resistance-associated protein 1 (ABCC1) and brain clearance of beta-amyloid (Aβ). We used PET with 6-bromo-7-[11C]methylpurine ([11C]BMP) to measure cerebral ABCC1 transport activity in a beta-amyloidosis mouse model (APP/PS1-21) and in wild-type mice aged 50 and 170 days, without and with pretreatment with the ABCC1 inhibitor MK571. One hundred seventy days-old-animals additionally underwent [11C]PiB PET scans to measure Aβ load. While baseline [11C]BMP PET scans detected no differences in the elimination slope of radioactivity washout from the brain (kelim) between APP/PS1-21 and wild-type mice of both age groups, PET scans after MK…
Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus e antigen and interferon-gamma are not injured by HBeAg specific au…
2000
Seroconversion from HBeAg to alphaHBe of persons chronically infected by HBV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these clinico-pathological features may be due to the activation of cytodestructive mechanisms by alphaHBe antibodies. The aim of the present study was to investigate the pathogenic potential of alphaHBe antibodies in a transgenic mouse model. Therefore, alphaHBe autoantibodies were elicited in double-transgenic mice expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon-gamma has reviously been shown to play an important role in the development of hepat…