Article
Microbiology
Yoshihiko Sakaguchi, Keiko Kobayashi, Masaya Takehara, Masahiro Nagahama
Summary: In this study, it was found that acid sphingomyelinase promotes the internalization of epsilon-toxin in MDCK cells. Blocking acid sphingomyelinase and exocytosis of lysosomes inhibited epsilon-toxin-induced vacuole formation. RNAi-mediated attenuation of acid sphingomyelinase blocked epsilon-toxin-induced vacuolation.
Article
Neurosciences
Liubov S. Kalinichenko, Laila Abdel-Hafiz, An-Li Wang, Christiane Muehle, Nadine Roesel, Fabian Schumacher, Burkhard Kleuser, Irena Smaga, Malgorzata Frankowska, Malgorzata Filip, Gerd Schaller, Tanja Richter-Schmidinger, Bernd Lenz, Erich Gulbins, Johannes Kornhuber, Andre W. C. Oliveira, Marilia Barros, Joseph P. Huston, Christian P. Mueller
Summary: The study found that sphingolipids play a crucial role in appetitively motivated learning and memory, with regionally enhanced neutral sphingomyelinase (NSM) activity being associated with superior performance. An opposite interaction was observed in aversively motivated tasks. NSM was confirmed to have a role in learning through its control of N-methyl-D-aspartate receptor subunit expression.
Review
Biochemistry & Molecular Biology
John W. Finnie, Francisco A. Uzal
Summary: Clostridium perfringens type D epsilon toxin (ETX) causes severe neurological disease in ruminant livestock and is of worldwide distribution. The toxin can reach the brain through the bloodstream, leading to neurologic syndromes. ETX is also listed as a potential bioterrorism agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Daniel G. P. Turner, Willem J. De Lange, Yanlong Zhu, Christopher L. Coe, Judith Simcox, Ying Ge, Timothy J. Kamp, J. Carter Ralphe, Alexey V. Glukhov
Summary: Cardiovascular disease, the leading cause of death in the USA, is aggravated by elevated mechanical stress from hypertension. This study investigates the loss of caveolae, plasma membrane structures that buffer mechanical stress, in pathological conditions associated with chronically stretched myocardium. The findings identify neutral sphingomyelinases (nSMase) as mechanoregulated mediators of caveolae loss, ceramide production, and blunted beta-adrenergic response in a human cardiac model.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Immunology
N. K. Gangwar, R. V. S. Pawaiya, K. Gururaj, Dimple Andani, R. Singh, A. Kumar, A. P. Singh
Summary: This study investigated the presence of epsilon toxin and beta 2 toxin in goat intestinal tissues, and found a strong association between these toxins and intestinal disorders in goats. Immunohistochemistry was shown to be a confirmatory tool for detecting bacterial toxins, especially epsilon toxin. Additionally, the pathogenic effects of cpb2 positive C. perfringens isolates in causing enterotoxaemia were explored. Further investigation is needed to understand the pathogenesis of enterotoxaemia in goats.
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Katerina Novotna, Ajit G. Thomas, Ondrej Stepanek, Brennan Murphy, Niyada Hin, Jan Skacel, Louis Mueller, Lukas Tenora, Arindom Pal, Jesse Alt, Ying Wu, James Paule, Rana Rais, Barbara S. Slusher, Takashi Tsukamoto
Summary: Neutral sphingomyelinase 2 (nSMase2) has been recognized as a therapeutic target to regulate ceramide production. A compound called larotrectinib, containing a pyrazolo[1,5-a]pyrimidine ring, was identified as an inhibitor of nSMase2. Further investigation revealed that N,N-dimethyl-5-morpholinopyrazolo[1,5-a]pyrimidin-3-amine showed potential as an orally available nSMase2 inhibitor with favorable pharmacokinetic properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Fabian Schumacher, Alexander Carpinteiro, Michael J. Edwards, Gregory C. Wilson, Simone Keitsch, Matthias Soddemann, Barbara Wilker, Burkhard Kleuser, Katrin Anne Becker, Christian P. Mueller, Johannes Kornhuber, Erich Gulbins
Summary: This study found that ceramide-enriched exosomes in the blood plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of these exosomes. Injection of microparticles from mice with MDD or injection of ceramide-loaded exosomes induce MDD-like behavior in untreated mice.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Food Science & Technology
Masahiro Nagahama, Keiko Kobayashi, Masaya Takehara
Summary: The study found that lysosomal proteases cathepsin B and L facilitate the internalization of iota-toxin by activating ASMase, indicating their role in the cytotoxicity caused by the toxin.
Article
Immunology
Mohammad Shokrzadeh, Ali Zeyar, Reza Golmohammadi, Seyed Hossein Mousavi, Seyed Ali Mirhosseini
Summary: The study found that Etx has significant oxidative stress effects on human lymphocytes at doses above 25 μM, and it significantly increases the number of micronuclei formed in lymphocytes. This indicates that Etx poses genetic toxicity and interferes with cell division processes.
MICROBIAL PATHOGENESIS
(2021)
Article
Biochemistry & Molecular Biology
Daniel Canals, Silvia Salamone, Bruno Jaime Santacreu, Daniel Aguilar, Maria Jose Hernandez-Corbacho, Anne G. Ostermeyer-Fay, Meaghan Greene, Erika Nemeth, John D. Haley, Lina M. Obeid, Yusuf A. Hannun
Summary: The study revealed that low doses of the chemotherapeutic compound doxorubicin result in dysregulation of cytoskeletal proteins, enhancing cancer cell migration, which could explain the reported effects of doxorubicin worsening cancer metastasis in animal models.
Article
Chemistry, Medicinal
Kan Yang, Keyi Nong, Fei Xu, Yu Chen, Jinying Yu, Lizhi Lin, Xiao Hu, Youzhi Wang, Ting Li, Jibin Dong, Jinxin Wang
Summary: In this study, a series of benzene-heterocyclic-based ASM inhibitors were designed, synthesized, and screened, and some compounds showed favorable inhibitory activity against recombinant human ASM. Compound 4i exhibited good pharmacokinetic properties and in vivo inhibitory activity against ASM, reducing the level of ceramide in mice plasma and liver. Moreover, 4i was found to decrease lipid plaques, plasma ceramide concentration, and Ox-LDL levels, and to regulate cell inflammation induced by LPS and Ox-LDL by modulating the levels of ceramide and sphingomyelin. Overall, this study demonstrates the potential of ASM as an effective target for treating atherosclerosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marie Gamal, Hatem Tallima, Hassan M. E. Azzazy, Anwar Abdelnaser
Summary: This study evaluated the effects of depleting total glutathione in HepG2 cells and found that it resulted in a significant decrease in the enzymatic activity of nSMase1 and nSMase3, an increase in ROS levels, a decrease in intracellular levels of ceramide, and an increase in cell proliferation. The study suggests that total glutathione depletion may aggravate liver cancer and does not support the use of total glutathione-depleting agents in HCC management. Further research is needed to confirm these effects in other cell lines and explore the role of total glutathione depletion in inducing tumor cell apoptosis.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Review
Clinical Neurology
Richard W. Titball, Nicholas Lewis, Richard Nicholas
Summary: Clostridium perfringens epsilon toxin is associated with enterotoxaemia in livestock and possibly plays a role in multiple sclerosis (MS) in humans. Strains of C. perfringens producing epsilon toxin are more likely to be found in the gut of MS patients and at higher levels, and MS patients are also more likely to have antibodies to epsilon toxin. The toxin damages the blood-brain barrier and brain cells expressing a specific receptor, leading to infiltration of immune cells and inducing an MS-like disease in an animal model. These findings suggest a role for epsilon toxin in MS, but further studies are needed to establish a causal relationship.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Article
Food Science & Technology
Wei Wan, Yue Li, Jing Wang, Zhiying Jin, Wenwen Xin, Lin Kang, Junhong Wang, Xiaoyang Li, Yakun Cao, Hao Yang, Jinglin Wang, Shan Gao
Summary: In this study, a new type of dissolving microneedle patch (dMN) with a nanoparticle adjuvant was developed to enhance immune response and deliver the rETX(Y196E)-C protein vaccine. The dMN vaccine showed good mechanical properties, immunogenicity, and protection, effectively preventing ETX poisoning.
Article
Biochemistry & Molecular Biology
Nuria Puig, Jose Rives, Montserrat Estruch, Ana Aguilera-Simon, Noemi Rotllan, Mercedes Camacho, Nuria Colome, Francesc Canals, Jose Luis Sanchez-Quesada, Sonia Benitez
Summary: Electronegative low-density lipoprotein (LDL(-)) is a modified fraction of human plasma LDL with atherogenic properties, including increased bioactive lipid mediator content. The present study suggests the presence of ceramidase (CDase)-like activity in LDL(-), which is associated with the increased sphingosine (Sph) content. However, the exact origin of this activity remains unknown and requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Philipp Grad, Katarina Edwards, Lars Gedda, Victor Agmo Hernandez
Summary: This study investigates the effects of polyethylene glycol-(PEG) modified lipids and gangliosides on the Ca2+ induced interaction between liposomes composed of palmitoyl-oleoyl phosphatidylethanolamine (POPE) and palmitoyl-oleoyl phosphatidylserine (POPS) at physiological ionic strength. The results show that naked liposomes tend to adhere, rupture, and collapse on each other's surfaces upon addition of Ca2+, eventually resulting in the formation of large multilamellar aggregates and bilayer sheets. However, the presence of gangliosides or PEGylated lipids leads to the formation of small, long-lived bilayer fragments/disks. PEGylated lipids seem to be more effective than gangliosides at stabilizing these structures. The study suggests that direct liposome-liposome fusion is not the dominating process triggered by Ca2+ in the systems studied.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Saurabh Saraswat, Archana Chugh
Summary: Cell penetrating peptides (CPP) are important tools for intracellular delivery of molecules. In this study, a novel marine-derived CPP from Engraulis japonicus, called Engraulisin, was reported. Engraulisin demonstrated successful cellular uptake and selective antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA), making it a potential candidate for drug delivery.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Emanuela Efodili, Ashlynn Knight, Maryem Mirza, Cedric Briones, Il-Hyung Lee
Summary: This study demonstrates the spontaneous transfer of small membrane-bound peptides between a supported lipid bilayer and giant unilamellar vesicles in vitro. The transfer occurs through the formation of hemi-fusion stalks and is limited to small peptides due to the highly curved structure of the stalk. This system provides a synthetic platform for studying peptide trafficking between synthetic membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Niu, Si Jia Chen, Jeffery B. Klauda
Summary: Macrophage membranes in the activated state are more tightly packed, exhibit increased chain order across lipid species, and form specific lipid clusters. These findings provide physiologically accurate models for future computational studies of macrophage membranes and their proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Niki Baccile, Vincent Chaleix, Ingo Hoffmann
Summary: This study measured the bending rigidity of self-assembled structures formed by a new biobased glucolipid bioamphiphile using neutron spin-echo (NSE) technology. The results showed that the bending rigidity of these structures is lower or higher compared to phospholipid membranes, providing a new theoretical basis for the application of these new molecular systems.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Alain Bolano Alvares, Pablo E. A. Rodriguez, Gerardo D. Fidelio
Summary: The behavior of amphiphilic molecules at the air/water interface was studied to evaluate the arrangement formed in a confined area. The surface properties of zwitterionic DPPC lipid and A beta(1-40) amyloid peptide in mixed films were investigated at different temperatures. DPPC undergoes a phase transition depending on temperature and lateral pressure, which allows for the study of its influence on amyloid structure formation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Lukasz Plachta, Marzena Mach, Magdalena Kowalska, Pawel Wydro
Summary: Resveratrol, a popular phytoalexin found in grapes and red wine, has beneficial effects on the cardiovascular system, exhibits antiviral, antibacterial, and antifungal properties, and may have therapeutic effects against cancer. This study investigates the interaction of resveratrol with model cell membranes, demonstrating changes in their physicochemical parameters and highlighting the role of cholesterol content in resveratrol incorporation. The findings suggest that the molecular mechanism of action of resveratrol may involve interactions with lipid rafts.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Edurne Rujas, Beatriz Apellaniz, Johana Torralba, David Andreu, Jose M. M. Caaveiro, Shixia Wang, Shan Lu, Jose L. Nieva
Summary: This study investigates the role of fusion peptide and Trp-rich membrane proximal external region in HIV-1 fusion and demonstrates that liposome-based formulations containing FP-MPER hybrid peptides can induce the production of specific neutralizing antibodies in rabbits. The results support the use of liposomes as vaccine carriers and the inclusion of lipid membranes in immunogens to elicit specific humoral responses.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Dailin Li, Dingyuan Shi, Lei Wang
Summary: G protein-gated inwardly rectifying potassium (GIRK) channels play a significant role in regulating cell excitability. This study investigated the ion permeation mechanism in GIRK2 mutants using molecular dynamic simulations and QM/MM methods. The results revealed the importance of a multi-ion distribution for ion conduction.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Max J. den Uijl, Arnold J. M. Driessen
Summary: Membrane protein insertion into and translocation across the bacterial cytoplasmic membrane are essential processes facilitated by the Sec translocon. The phospholipid dependence of membrane protein insertion has remained mostly unknown. This study reveals that the insertion of the mannitol permease MtlA into the membrane depends on the presence of phosphatidylglycerol and is stimulated by phosphatidylethanolamine.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick Allen, Adam C. Smith, Vernon Benedicto, Abbas Abdulhasan, Vasanthy Narayanaswami, Enrico Tapavicza
Summary: We explore the stability, size, and structure of nanodiscs formed by the N-terminal domain of apolipoprotein E3 and a variable number of 1,2-dimyristoyl-sn-glycero-3-phosphocholine molecules. Our simulations suggest that nanodiscs containing 240 to 420 DMPC molecules are stable. The antiparallel configuration shows more protein-protein interactions and ionic contacts, as well as greater stability and rigidity compared to the parallel configuration.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick M. Keating, Nicholas P. Schifano, Xinrui Wei, Matthew Y. Kong, Jinwoo Lee
Summary: Lassa virus (LASV) infection is dependent on the fusion of its viral membrane with the host cell membrane, and our study reveals that this fusion process involves pH-dependent conformational changes in the transmembrane domain of LASV. These findings provide valuable insights into the fusion mechanism of LASV and can be utilized in the design of therapeutics to combat Lassa virus infections and prevent its potential spread.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Ashley L. Bennett, Kristen N. Cranford, Austin L. Bates, Christopher R. Sabatini, Hee-Seung Lee
Summary: This study employed molecular dynamics simulations to elucidate the binding, folding, and insertion details of TP10W in the cell membrane. The simulations revealed that TP10W can translocate across the lipid membrane as a monomer, and the charged amino acid side chains can move between lipid leaflets. Comparison with point mutated variants demonstrated significant conformational changes due to charge distribution.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Jessica H. van Wonderen, Jason C. Crack, Marcus J. Edwards, Thomas A. Clarke, Gerhard Saalbach, Carlo Martins, Julea N. Butt
Summary: Electrogenic bacteria transfer excess respiratory electrons to metal oxide particles and electrodes through the MtrCAB complex. The crystal structure of MtrCAB from S. baltica OS185 was resolved, and liquid chromatography mass spectrometry was used to determine the mass values of the three proteins in purified MtrCAB complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Review
Biochemistry & Molecular Biology
Yi-Ming Chen, Ching-Tai Lu, Chia-Wen Wang, Wolfgang B. Fischer
Summary: A series of dye ligands were ranked based on docking experiments, selecting the most suitable ligands for binding with different proteins. Additionally, a comparison study was conducted on a series of repurposing drugs and known antivirals.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)