Nathan Bulangalire, Charlotte Claeyssen, Onnik Agbulut, Caroline Cieniewski-Bernard
Small Heat Shock Proteins are considered as the first line of defense when proteostasis fails. Among them, αB-crystallin is expressed in striated muscles in which it interacts with desmin intermediate filaments to stabilize them, maintaining cytoskeleton's integrity and muscular functionalities. Desmin is a key actor for muscle health; its targeting by αB-crystallin is thus crucial, especially in stress conditions. αB-crystallin is phosphorylated and O-GlcNAcylated. Its phosphorylation increases consecutively to various stresses, correlated with its recruitment for cytoskeleton's safeguarding...
April 16, 2024: Biochimie
Paolo Cascio
PA28γ is a proteasomal interactor whose main and most known function is to stimulate the hydrolytic activity of the 20S proteasome independently of ubiquitin and ATP. Unlike its two paralogues, PA28α and PA28β, PA28γ is largely present in the nuclear compartment and plays pivotal functions in important pathways such as cellular division, apoptosis, neoplastic transformation, chromatin structure and organization, fertility, lipid metabolism, and DNA repair mechanisms. Although it is known that a substantial fraction of PA28γ is found in the cell in a free form (i...
April 15, 2024: Biochimie
Gimena Salas, Alen A Litta, Anabela C Medeot, Virginia Schuck, Romina B Andermatten, Gisel S Miszczuk, Nadia Ciriaci, Ma Valeria Razori, Ismael R Barosso, Enrique J Sánchez Pozzi, Marcelo G Roma, Cecilia L Basiglio, Fernando A Crocenzi
The endogenous metabolite of estradiol, estradiol 17β-D-glucuronide (E17G), is considered the main responsible of the intrahepatic cholestasis of pregnancy. E17G alters the activity of canalicular transporters through a signaling pathway-dependent cellular internalization, phenomenon that was attributed to oxidative stress in different cholestatic conditions. However, there are no reports involving oxidative stress in E17G-induced cholestasis, representing this the aim of our work. Using polarized hepatocyte cultures, we showed that antioxidant compounds prevented E17G-induced Mrp2 activity alteration, being this alteration equally prevented by the NADPH oxidase (NOX) inhibitor apocynin...
April 10, 2024: Biochimie
Rilès Boumali, Laureline Urli, Meriem Naim, Feryel Soualmia, Kiyoka Kinugawa, Isabelle Petropoulos, Chahrazade El Amri
Alzheimer's disease (AD) and related dementias constitute an important global health challenge. Detailed understanding of the multiple molecular mechanisms underlying their pathogenesis constitutes a clue for the management of the disease. Kallikrein-related peptidases (KLKs), a lead family of serine proteases, have emerged as potential biomarkers and therapeutic targets in the context of AD and associated cognitive decline. Hence, KLKs were proposed to display multifaceted impacts influencing various aspects of neurodegeneration, including amyloid-beta aggregation, tau pathology, neuroinflammation, and synaptic dysfunction...
April 10, 2024: Biochimie
Hasana Baber, Arega Aghajani, B Harold Gallimore, Cassandra Bethel, James G Hyatt, Elizabeth F B King, Helen P Price, Marissa L Maciej-Hulme, Suat Sari, Anja Winter
Leishmaniasis is a spectrum of conditions caused by infection with the protozoan Leishmania spp. parasites. Leishmaniasis is endemic in 98 countries around the world, and resistance to current anti-leishmanial drugs is rising. Our work has identified and characterised a previously unstudied galactokinase-like protein (GalK) in Leishmania donovani, which catalyses the MgATP-dependent phosphorylation of the C-1 hydroxyl group of d-galactose to galactose-1-phosphate. Here, we report the production of the catalytically active recombinant protein in E...
April 3, 2024: Biochimie
J Michael Conlon, Ananyaa Sridhar, Dawood Khan, Taylor S Cunning, Jack J Delaney, Megan G Taggart, Nigel G Ternan, Jérôme Leprince, Laurent Coquet, Thierry Jouenne, Samir Attoub, Milena Mechkarska
Five host-defense peptides (figainin 2PL, hylin PL, raniseptin PL, plasticin PL, and peptide YL) were isolated from norepinephrine-stimulated skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae) collected in Trinidad. Raniseptin PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH2 ) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQP KQ.NH2 ) showed potent and rapid bactericidal activity against a range of clinically relevant Gram-positive and Gram-negative ESKAPE +  pathogens and Clostridioides difficile...
March 30, 2024: Biochimie
Johannes Schneider, Julia Mitschke, Mahima Bhat, Daniel Vogele, Oliver Schilling, Thomas Reinheckel, Lisa Heß
Cathepsin D (CTSD) is a lysosomal aspartic protease and its inherited deficiency causes a severe pediatric neurodegenerative disease called neuronal ceroid lipofuscinosis (NCL) type 10. The lysosomal dysfunction in the affected patients leads to accumulation of undigested lysosomal cargo especially in none-dividing cells, such as neurons, resulting in death shortly after birth. To explore which proteins are mainly affected by the lysosomal dysfunction due to CTSD deficiency, Lund human mesencephalic (LUHMES) cells, capable of inducible dopaminergic neuronal differentiation, were treated with Pepstatin A...
March 27, 2024: Biochimie
Maria M Oliveira, Sofia Correia, Cecilia Peirone, Marques Magalhães, Paula Oliveira, Francisco Peixoto
Ozone therapy's efficacy might stem from the regulated and mild oxidative stress resulting from ozone's interactions with various biological elements. The present work aimed to characterize the hepatic mitochondrial response to ozone treatment and its relationship with the antioxidant system response. Two groups of mice were used: one control group and another injected intraperitoneally with an O3 /O2 mixture (80 ml/kg) for 5 days. Mitochondrial respiration supported by different substrates was significantly inhibited, as well as complexes I and II/III, but not complex IV...
March 26, 2024: Biochimie
Samuel Barbosa, Mafalda Barbosa Pedrosa, Rita Ferreira, Daniel Moreira-Gonçalves, Lúcio Lara Santos
The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models...
March 25, 2024: Biochimie
Shuo Li, Huijia Song, Yanping Sun, Yongjun Sun, Huimin Zhang, Zibin Gao
The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases...
March 24, 2024: Biochimie
Nathalie Vergnolle
Many studies have demonstrated the involvement of proteases in gut physiology and pathophysiology over the recent years. Among them, thrombin has appeared for a long time as an old player only involved in blood clotting upon tissue injury. The fact that thrombin receptors (Protease-Activated Receptors-1 and -4) are expressed and functional in almost all cell types of the gut, contributing to barrier, immune or motility functions, suggested that thrombin could actually be at the crossroad of intestinal physiology...
March 21, 2024: Biochimie
Heidi Kyung Noddeland, Vahap Canbay, Marianne Lind, Simonas Savickas, Louise Bastholm Jensen, Karsten Petersson, Martin Malmsten, Janne Koch, Ulrich Auf dem Keller, Andrea Heinz
Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics...
March 19, 2024: Biochimie
Jean A Boutin, Valérie Hamon de Almeida, Nathalie Coussay, Céline Legros, Gilles Ferry, Karine Reybier
Among the properties melatonin is claimed to possess, are the immuno-inflammation inductive capacities that would be responsible of some of the paramount of activities melatonin is reported to have in most of the human pathological conditions. In the present paper, we measured the effect of melatonin on established cellular models of immuno-inflammation, and found none. The discrepancies are discussed, especially because those properties are reported at pharmacological concentration (1 μM and beyond) at which the melatonin receptors are desensitized by internalization, leading to putative non-receptor-dependent mechanism of action...
March 18, 2024: Biochimie
Farid Nasiri, Parisa Ebrahimi, Mohammad Bagher Shahsavani, Anis Barati, Issa Zarei, Jun Hong, Masaru Hoshino, Ali Akbar Moosavi-Movahedi, Reza Yousefi
To date, several pathogenic mutations have been identified in the primary structure of human α-Crystallin, frequently involving the substitution of arginine with a different amino acid. These mutations can lead to the incidence of cataracts and myopathy. Recently, an important cataract-associated mutation has been reported in the functional α-Crystallin domain (ACD) of human αB-Crystallin protein, where arginine 107 (R107) is replaced by a leucine. In this study, we investigated the structure, chaperone function, stability, oligomerization, and amyloidogenic properties of the p...
March 15, 2024: Biochimie
Sulfath Thottungal Parambil, Gisha Rose Antony, Ajeesh Babu Littleflower, Lakshmi Subhadradevi
The incidence of breast cancer is perpetually growing globally, and it remains a major public health problem and the leading cause of mortality in women. Though the aberrant activities of the Hippo pathway have been reported to be associated with cancer, constructive knowledge of the pathway connecting the various elements of breast cancer remains to be elucidated. The Hippo transducers, yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ), are reported to be either tumor suppressors, oncogenes, or independent prognostic markers in breast cancer...
March 15, 2024: Biochimie
Rajas M Rao, Ibaa El Dhaybi, Frédéric Cadet, Catherine Etchebest, Julien Diharce
Translocator protein (TSPO) is an 18 kDa transmembrane protein, localized primarily on the outer mitochondrial membrane. It has been found to be involved in various physiological processes and pathophysiological conditions. Though studies on its structure have been performed only recently, there is little information on the nature of dynamics and doubts about some structures referenced in the literature, especially the NMR structure of mouse TSPO. In the present work, we thoroughly study the dynamics of mouse TSPO protein by means of atomistic molecular dynamics simulations, in presence as well as in absence of the diagnostic ligand PKA...
March 15, 2024: Biochimie
Florent Estur, Emilie Murigneux, Alexis David, Mélia Magnen, Ahlame Saidi, Gilles Lalmanach, Fabien Lecaille
A long-term exposure to cigarette smoke (CS) alters the integrity of airway epithelial barrier, contributes to lung dysfunction, and elicits the expression and activity of lung cathepsin S (CatS), a cysteine protease that participates in the remodeling of connective tissue and cell junctions. Here, we observed that a short-term (4 days) exposure of mice to CS increased the expression and activity of CatS, while the expression level of zonula occludens 1 (ZO-1), an epithelial tight junction protein that stabilizes barrier assembly, was reduced in lung tissue lysates...
March 15, 2024: Biochimie
Tatiana A Filippova, Rami A Masamrekh, Yulia Yu Khudoklinova, Victoria V Shumyantseva, Alexey V Kuzikov
We discuss the diverse functions of proteases in the context of their biotechnological and medical significance, as well as analytical approaches used to determine the functional activity of these enzymes. An insight into modern approaches to studying the kinetics and specificity of proteases, based on spectral (absorption, fluorescence), mass spectrometric, immunological, calorimetric, and electrochemical methods of analysis is given. We also examine in detail electrochemical systems for determining the activity and specificity of proteases...
March 15, 2024: Biochimie
Samuel Zolg, Laura Donzelli, Ruth Geiss-Friedlander
Dipeptidyl peptidase 9 (DPP9) is an intracellular amino-dipeptidase with physiological roles in the immune system, DNA repair and mitochondria homeostasis, while its deregulation is linked to cancer progression and immune-associated defects. Through its rare ability to cleave a peptide bond following the imino-acid proline, DPP9 acts as a molecular switch that regulates key proteins, such as the tumor-suppressor BRCA2. In this review we will discuss key concepts underlying the outcomes of protein processing by DPP9, including substrate turn-over by the N-degron pathway...
March 8, 2024: Biochimie
Maria Monticelli, Bruno Hay Mele, Demi Marie Wright, Simone Guerriero, Giuseppina Andreotti, Maria Vittoria Cubellis
PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches. We used Recombinant Bacterial Thermal Shift Assay to assess the binding of a substrate analog to phosphomannomutase-2 and the specific binding to phosphomannomutase-1 of an FDA-approved drug - clodronate...
March 6, 2024: Biochimie
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