The Imidazolium Ionic Liquids Toxicity is Due to Their Effect on the Plasma Membrane
AbstractIonic liquids (ILs) are organic salts with a low melting point. This is due to the fact that their alkyl side chains, which are covalently connected to the ion, hinder the crystallization of ILs. The low melting point of ILs has led to their widespread use as relatively harmless solvents. However, ILs do have toxic properties, the mechanism of which is largely unknown, so identifying the cellular targets of ILs is of practical importance. In our work, we showed that imidazolium ILs are not able to penetrate model membranes without damaging them. We also found that inactivation of multidrug resistance (MDR) pumps ...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Investigation of Potential Effects of Some Indole Compounds on the Glutathione S-Transferase Enzyme
AbstractGlutathione S-transferases (GSTs) belong to the superfamily of multifunctional detoxification isoenzymes with an important role in cellular signaling. They can prevent reactive electrophilic compounds from harming the body by covalently binding identical type of moleculs to each other. GSTs can be used alone or in combination for cancer detection or diagnosis, in addition to therapeutic interventions. In recent years, indoles have become important due to their structural properties and biological activities such as antitubercular, antiulcer, anti-oxidant, and antidiabetic, as well as for the development of new anti...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Overexpression of the limk1 Gene in Drosophila melanogaster Can Lead to Suppression of Courtship Memory in Males
AbstractCourtship suppression is a behavioral adaptation of the fruit fly. When majority of the females in a fly population are fertilized and non-receptive for mating, a male, after a series of failed attempts, decreases its courtship activity towards all females, saving its energy and reproductive resources. The time of courtship decrease depends on both duration of unsuccessful courtship and genetically determined features of the male nervous system. Thereby, courtship suppression paradigm can be used for studying molecular mechanisms of learning and memory. p-Cofilin, a component of the actin remodeling signaling casca...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
The Impact of Long-Term Hypoxia on the Antioxidant Defense System in the Siberian Frog Rana amurensis
AbstractThe Siberian frogRana amurensis has a uniquely high tolerance to hypoxia among amphibians, as it is able to withstand several months underwater with almost no oxygen (0.2 mg/liter) vs. several days for other studied species. Since it was hypothesized that hypoxia actives the antioxidant defense system in hypoxia-tolerant animals, one would expect similar response inR. amurensis. Here, we studied the effect of hypoxia in the Siberian frog based on the transcriptomic data, activities of antioxidant enzyme, and content of low-molecular-weight antioxidants. Exposure to hypoxia upregulated expression of three relevan...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Pro-Inflammatory Activation Suppresses TRAIL-induced Apoptosis of Acute Myeloid Leukemia Cells
In this study, we investigated mechanisms of this phenomenon using Western blot analysis, caspase 3 enzymatic activity analysis, quantitative reverse transcription-PCR, and flow cytometry. The results showed that the increased resistance to the TRAIL- induced cell death of AML THP-1 cells during their pro-inflammatory activation is associated with the decrease in the surface expression of the proapoptotic receptors TRAIL-R1/DR4 and TRAIL-R2/DR5, as well as with the increased content of members of the IAPs family – Livin and cIAP2. The results of this article open up new insights into the role of inflammation in formati...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Effect of Focal Adhesion Kinase and Vinculin Expression on Migration Parameters of Normal and Tumor Epitheliocytes
AbstractFocal adhesions (FAs) are mechanosensory structures that transform physical stimuli into chemical signals guiding cell migration. Comprehensive studies postulate correlation between the FA parameters and cell motility metrics for individual migrating cells. However, which properties of the FAs are critical for epithelial cell motility in a monolayer remains poorly elucidated. We used high-throughput microscopy to describe relationship between the FA parameters and cell migration in immortalized epithelial keratinocytes (HaCaT) and lung carcinoma cells (A549) with depleted or inhibited vinculin and focal adhesion ki...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Role of the Gut Microbiome and Bacterial Amyloids in the Development of Synucleinopathies
AbstractLess than ten years ago, evidence began to accumulate about association between the changes in the composition of gut microbiota and development of human synucleinopathies, in particular sporadic form of Parkinson ’s disease. We collected data from more than one hundred and thirty experimental studies that reported similar results and summarized the frequencies of detection of different groups of bacteria in these studies. It is important to note that it is extremely rare that a unidirectional change in the population of one or another group of microorganisms (only an elevation or only a reduction) was detected i...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Protective Activity of Inactivated Rabies Vaccine Using Flagellin-Based Adjuvant
In this study, the ability of an adjuvant based on recombinantSalmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats “Rabikan” (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the m ost widely used and internationally recommended method for testing effectiveness of...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Human Blood Serum Counteracts EGFR/HER2-Targeted Drug Lapatinib Impact on Squamous Carcinoma SK-BR-3 Cell Growth and Gene Expression
AbstractLapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line. This antagonism between lapatinib and human serum was associated with cancelation of the drug i nduced G1/S cell cycle transition arrest. RNA sequencing revealed 308 differentially expressed genes in th...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Oxidative Stress-Induced Platelet Apoptosis/Activation: Alleviation by Purified Curcumin via ASK1-JNK/p-38 Pathway
AbstractPlatelets are known for their indispensable role in hemostasis and thrombosis. However, alteration in platelet function due to oxidative stress is known to mediate various health complications, including cardiovascular diseases and other health complications. To date, several synthetic molecules have displayed antiplatelet activity; however, their uses are associated with bleeding and other adverse effects. The commercially available curcumin is generally a mixture of three curcuminoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Although crude curcumin is known to inhibit platelet aggregation, the effe...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Role of I182, R187, and K188 Amino Acid Residues in the Catalytic Domain of HIV-1 Integrase in the Processes of Reverse Transcription and Integration
AbstractStructural organization of HIV-1 integrase is based on a tetramer formed by two protein dimers. Within this tetramer, the catalytic domain of one subunit of the first dimer interacts with the N-terminal domain of the second dimer subunit. It is the tetrameric structure that allows both ends of the viral DNA to be correctly positioned relative to the cellular DNA and to realize catalytic functions of integrase, namely 3 ′-processing and strand transfer. However, during the HIV-1 replicative cycle, integrase is responsible not only for the integration stage, it is also involved in reverse transcription and is neces...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Novel Gain-of-Function Mutation in the Kv11.1 Channel Found in the Patient with Brugada Syndrome and Mild QTc Shortening
AbstractBrugada syndrome (BrS) is an inherited disease characterized by right precordial ST-segment elevation in the right precordial leads on electrocardiograms (ECG), and high risk of life-threatening ventricular arrhythmia and sudden cardiac death (SCD). Mutations in the responsible genes have not been fully characterized in the BrS patients, except for theSCN5A gene. We identified a new genetic variant, c.1189C>T (p.R397C), in theKCNH2 gene in the asymptomatic male proband diagnosed with BrS and mild QTc shortening. We hypothesize that this variant could alter IKr-current and may be causative for the rare non-SCN5A...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Structure- and Cation-Dependent Mechanism of Interaction of Tricyclic Antidepressants with NMDA Receptor According to Molecular Modeling Data
AbstractSome tricyclic antidepressants (TCAs), including amitriptyline (ATL), clomipramine (CLO), and desipramine (DES), are known to be effective for management of neuropathic pain. It was previously determined that ATL, CLO, and DES are capable of voltage-dependent blocking of NMDA receptors of glutamate (NMDAR), which play a key role in pathogenesis of neuropathic pain. Despite the similar structure of ATL, CLO, and DES, efficacy of their interaction with NMDAR varies significantly. In the study presented here, we applied molecular modeling methods to investigate the mechanism of binding of ATL, CLO, and DES to NMDAR an...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis
AbstractThe contents of homocysteine (HCy), cyanocobalamin (vitamin B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of theMTHFR gene, A2756G of theMTR gene and A66G of theMTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant incr...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
The Mechanism of Inhibition of Mycobacterial (p)ppGpp Synthetases by a Synthetic Analog of Erogorgiaene
This study might help in the development of alarmone synthetase inhibitors, which includes relacin and its derivatives, as well as DMNP – a synthetic analog of the marine coral metabolite erogorgiaene. Unlike conventional antibiotics, alarmone synthetase inhibitors target metabolic pathways linked to the bacterial stringent response. Although these pathways are not essential for bacteria, they regulate the development of adaptat ion mechanisms. Combining conventional antibiotics that target actively growing cells with compounds that impede bacterial adaptation may address challenges associated with antimicrobial resist...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research
