Search results for "Peptide"

Prostaglandin E2 and prostaglandin F2 alpha as endometrial receptivity biomarkers in successful embryo implantation

2014

Failure in the adhesion of the human blastocyst to the endometrium has been described as an important cause of infertility. Establishing the period of the so-called window of implantation and understanding the molecular mechanisms associated with embryo implantation has clinical and scientific implications. While over the last decades histological evaluation has been used to determine the phase of the menstrual cycle of the endometrium, the poor information obtained has made the case of using new technologies to identify specific markers, understand and characterize the receptive stage. This doctoral thesis investigates the existence, function and clinical impact of two specific lipids, the…

Transport of Arabidopsis GPI-anchored proteins along the early secretory pathway: Role of GPI-anchor remodelling and p24 proteins

2019

Las proteínas con anclaje GPI son una familia de proteínas que están ancladas a la cara exterior de la membrana plasmática mediante un ancla GPI y se ha visto que juegan un papel clave en plantas. Sin embargo, la maquinaria molecular implicada en el transporte de estas proteínas a la membrana plasmática en plantas es aún desconocida. Las proteínas p24 tienen un papel importante en el control de calidad de proteínas (posiblemente incluyendo las proteínas con anclaje GPI) transportadas entre el Retículo Endoplasmático y el aparato de Golgi. Esta tesis doctoral tiene como objetivo el estudio de la posible implicación de las proteínas p24 en la salida del Retículo Endoplasmático y en la localiz…

Exploring fast proton transfer events associated with lateral proton diffusion on the surface of membranes

2019

Proton diffusion (PD) across biological membranes is a fundamental process in many biological systems, and much experimental and theoretical effort has been employed for deciphering it. Here, we report on a spectroscopic probe, which can be tightly tethered to the membrane, for following fast (nanosecond) proton transfer events on the surface of membranes. Our probe is composed of a photoacid that serves as our light-induced proton source for the initiation of the PD process. We use our probe to follow PD, and its pH dependence, on the surface of lipid vesicles composed of a zwitterionic headgroup, a negative headgroup, a headgroup that is composed only from the negative phosphate group, or…

RAB18 Loss Interferes With Lipid Droplet Catabolism and Provokes Autophagy Network Adaptations

2020

Autophagy is dependent on appropriate lipid supply for autophagosome formation. The regulation of lipid acquisition and the autophagy network response to lipid-limiting conditions are mostly elusive. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet catabolism, causing an impaired fatty acid release. The resulting reduced lipid-droplet-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network. These adjustments include increased expression and phosphorylation of ATG2B as well as augmented formation of the ATG12-ATG5 conjugate. Moreover, ATG9A shows an enhanced phosphorylation at amino acid residues tyrosi…

Inhibition of Rac1 signaling by lovastatin protects against anthracycline-induced cardiac toxicity

2011

Normal tissue damage limits the efficacy of anticancer therapy. For anthracyclines, the clinically most relevant adverse effect is cardiotoxicity. The mechanisms involved are poorly understood and putative cardioprotectants are controversially discussed. Here, we show that the lipid-lowering drug lovastatin protects rat H9c2 cardiomyoblasts from doxorubicin in vitro. Protection by lovastatin is related to inhibition of the Ras-homologous GTPase Rac1. It rests on a reduced formation of DNA double-strand breaks, resulting from the inhibition of topoisomerase II by doxorubicin. Doxorubicin transport and reactive oxygen species are not involved. Protection by lovastatin was confirmed in vivo. I…

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…

2006

Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…

Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis.

2005

Objective— Sedentary lifestyle is associated with increased cardiovascular events. The underlying molecular mechanisms are incompletely understood. Reactive oxygen species (ROS) contribute to endothelial dysfunction and atherosclerosis. An important source of vascular ROS is the NADPH oxidase. Methods and Results— C57BL6 mice were subjected to regular housing (physical inactivity) or voluntary training on running wheels (6 weeks). Inactivity increased vascular lipid peroxidation to 148±9% and upregulated superoxide release to 176±17% (L-012 chemiluminescence) and 188±29% (cytochrome C reduction assay), respectively. ROS production was predominantly increased in the endothelium and the medi…

Evidence for region-specific effects of glucagone-like peptide-2 in mouse stomach

2009

Regulation of the HTRA2 Protease Activity by an Inhibitory Antibody-Derived Peptide Ligand and the Influence on HTRA2-Specific Protein Interaction Ne…

2021

The mitochondrial serine protease HTRA2 has many versatile biological functions ranging from being an important regulator of apoptosis to being an essential component for neuronal cell survival and mitochondrial homeostasis. Loss of HTRA2 protease function is known to cause neurodegeneration, whereas overactivation of its proteolytic function is associated with cell death and inflammation. In accordance with this, our group verified in a recent study that the synthetic peptide ASGYTFTNYGLSWVR, encoding the hypervariable sequence part of an antibody, showed a high affinity for the target protein HTRA2 and triggered neuroprotection in an in vitro organ culture model for glaucoma. To unravel t…

Dietary fatty acids in the retina: beyond DHA, is EPA the underestimate intermediate?

2016

Dietary fatty acids in the retina: beyond DHA, is EPA the underestimate intermediate?. 12. congress of the international society for the study of fatty acids and lipids