Subhajit Chakraborty, Jagdish Mishra, Ankan Roy, Niharika Niharika, Soumen Manna, Tirthankar Baral, Piyasa Nandi, Subhajit Patra, Samir Kumar Patra
Liquid-liquid phase separation (LLPS) describes many biochemical processes, including hydrogel formation, in the integrity of macromolecular assemblages and existence of membraneless organelles, including ribosome, nucleolus, nuclear speckles, paraspeckles, promyelocytic leukemia (PML) bodies, Cajal bodies (all exert crucial roles in cellular physiology), and evidence are emerging day by day. Also, phase separation is well documented in generation of plasma membrane subdomains and interplay between membranous and membraneless organelles...
May 7, 2024: Biochimie
M van de Vyver, R M Benecke, L van den Heuvel, M J Kruger, Y Powrie, S Seedat, C Smith
Incidence of mental health disorders are rising in modernity, with psychological stress linked to a propensity for developing various chronic diseases due to a relative inability of the body to counter the allostatic load on cellular level. Despite these high rates of comorbidities associated with posttraumatic stress disorder (PTSD), there is still a lack of understanding in terms of the peripheral effects of PTSD on tissue level. Therefore, the purpose of this study was to profile basal dermal fibroblast functional status in PTSD using a wide range of markers involved in the cell-to-cell communication facilitated by fibroblasts...
May 6, 2024: Biochimie
Aylin Erman, Liam J Hawkins, Kenneth B Storey
During the hibernation season, the thirteen-lined ground squirrel undergoes cyclical torpor and arousal periods. The decrease and restoration of metabolic rate and oxygen delivery during torpor and arousal, respectively, may cause reperfusion-ischemia injury in the kidneys. In order to maintain the structural integrity of the kidneys necessary for renal function resumption during arousal, the thirteen-lined ground squirrel has developed adaptive methods to prevent and repair kidney injury. In this present study, computational methods were used to clean and analyze sequenced kidney RNA samples...
May 3, 2024: Biochimie
George A Saratov, Alexey A Belogurov, Anna A Kudriaeva
Inhibition of autophagy is one of the hallmarks of the SARS-CoV-2 infection. Recently it was reported that SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes via interaction with VPS39 thus preventing binding of homotypic fusion and protein sorting (HOPS) complex to RAB7 GTPase. Here we report that myelin basic protein (MBP), a major structural component of the myelin sheath, binds ORF3a and is colocalized with it in mammalian cells. Co-expression of MBP with ORF3a restores autophagy in mammalian cells, inhibited by viral protein...
May 2, 2024: Biochimie
Christelle Saade, Alexandre Pozza, Françoise Bonnete, Stéphanie Finet, Viviane Lutz-Bueno, Mark D Tully, Paloma F Varela, Jean-Jacques Lacapere, Sophie Combet
TSPO is a ubiquitous transmembrane protein used as a pharmacological marker in neuroimaging. The only known atomic structure of mammalian TSPOs comes from the solution NMR of mouse TSPO (mTSPO) bound to the PK11195 ligand and in a DPC surfactant environment. No structure is available in a biomimetic environment and without PK11195 which strongly stiffens the protein. We measured the effect of different amphiphilic environments on ligand-free mTSPO to study its structure/function and find optimal solubilization conditions...
April 23, 2024: Biochimie
Urša Pečar Fonović, Janko Kos, Ana Mitrović
Cathepsins, a family of lysosomal peptidases, play a crucial role in maintaining cellular homeostasis by regulating protein turnover and degradation as well as many specific regulatory actions that are important for proper cell function and human health. Alterations in the activity and expression of cathepsins have been observed in many diseases such as cancer, inflammation, neurodegenerative disorders, bone remodelling-related conditions and others. These changes are not exclusively harmful, but rather appear to be a compensatory response on the lack of one cathepsin in order to maintain tissue integrity...
April 23, 2024: Biochimie
Hailey N Swain, Parker D Boyce, Bradley A Bromet, Kaiden Barozinksy, Lacy Hance, Dakota Shields, Gayla R Olbricht, Julie A Semon
Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential...
April 22, 2024: Biochimie
Larissa Daniele Bobermin, Daniele Schauren da Costa, Aline Daniel Moreira de Moraes, Vanessa Fernanda da Silva, Giancarlo Tomazzoni de Oliveira, Patrícia Sesterheim, Ana Carolina Tramontina, Luiz Augusto Basso, Guilhian Leipnitz, André Quincozes-Santos, Carlos-Alberto Gonçalves
Astrocytes are glial cells that play key roles in neuroinflammation, which is a common feature in diabetic encephalopathy and aging process. Metformin is an antidiabetic compound that shows neuroprotective properties, including in inflammatory models, but astroglial signaling pathways involved are still poorly known. Interferons α/β are cytokines that participate in antiviral responses and the lack of their signaling increases susceptible to viral infections. Here, we investigated the effects of metformin on astrocytes from hypothalamus, a crucial brain region related to inflammatory processes...
April 18, 2024: Biochimie
Julia Buggiani, Thierry Meinnel, Carmela Giglione, Frédéric Frottin
The proteostasis network and associated protein quality control (PQC) mechanisms ensure proteome functionality and are essential for cell survival. A distinctive feature of eukaryotic cells is their high degree of compartmentalization, requiring specific and adapted proteostasis networks for each compartment. The nucleus, essential for maintaining the integrity of genetic information and gene transcription, is one such compartment. While PQC mechanisms have been investigated for decades in the cytoplasm and the endoplasmic reticulum, our knowledge of nuclear PQC pathways is only emerging...
April 18, 2024: Biochimie
Martina Gyimesi, Lotta E Oikari, Chieh Yu, Heidi G Sutherland, Dale R Nyholt, Lyn R Griffiths, Andre J Van Wijnen, Rachel K Okolicsanyi, Larisa M Haupt
Stem cell therapies hold promise in addressing the burden of neurodegenerative diseases with human embryonic neural stem cells (hNSC-H9s) and bone marrow-derived human mesenchymal stem cells (hMSCs) as viable candidates. The induction of hMSC neurospheres (hMSC-IN) generate a more lineage-restricted common neural progenitor-like cell population, potentially tunable by heparan sulfate proteoglycans (HSPGs). We examined CpG (5mC) site methylation patterns using Illumina Infinium 850K EPIC arrays in hNSC-H9, hMSCs and hMSC-IN cultures with HSPG agonist heparin at early and late phases of growth...
April 17, 2024: Biochimie
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
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