Glucose transporter 5 (GLUT5) overexpression has gained increasing attention due to its profound implications for tumorigenesis. This manuscript provides a comprehensive overview of the key findings and implications associated with GLUT5 overexpression in cancer. GLUT5 has been found to be upregulated in various cancer types, leading to alterations in fructose metabolism and enhanced glycolysis, even in the presence of oxygen, a hallmark of cancer cells.
View Article and Find Full Text PDFThis manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of K channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of K activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.
View Article and Find Full Text PDFIon channels activity is regulated through soluble guanylate cyclase (sGC) and adenylate cyclase (AC) pathways, while phosphodiesterases (PDE) control the intracellular levels of cAMP and cGMP. Here we applied RNA transcriptome sequencing to study changes in the gene expression of the sGC, AC, and PDE isoforms in isolated rat ventricular cardiomyocytes under conditions of microgravity and hypergravity. Our results demonstrate that microgravity reduces the expression of sGC isoform genes, while hypergravity increases their expression.
View Article and Find Full Text PDFHuman cardiac fibroblasts (HCFs) have mRNA transcripts that encode different mechanosensitive ion channels and channel regulatory proteins whose functions are not known yet. The primary goal of this work was to define the mechanosensitive ion channelome of HCFs. The most common type of cationic channel is the transient receptor potential (TRP) family, which is followed by the TWIK-related K channel (TREK), transmembrane protein 63 (TMEM63), and PIEZO channel (PIEZO) families.
View Article and Find Full Text PDFThe mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart's morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment.
View Article and Find Full Text PDFEF24, a synthetic monocarbonyl analog of curcumin, shows significant potential as an anticancer agent with both chemopreventive and chemotherapeutic properties. It exhibits rapid absorption, extensive tissue distribution, and efficient metabolism, ensuring optimal bioavailability and sustained exposure of the target tissues. The ability of EF24 to penetrate biological barriers and accumulate at tumor sites makes it advantageous for effective cancer treatment.
View Article and Find Full Text PDFSince hypergravity changes the morphological and physiological properties of the heart, it was assumed that the expression of ion channels that respond to cell stretching or compressing, mechanically gated channels (MGC) and mechanosensitive channels (MSC), would be affected. Using RNA transcriptome sequencing, the change in the number of transcripts for MGC and MSC genes was studied in isolated rat ventricular cardiomyocytes under 4g hypergravity for 5 days. It was shown for the first time that hypergravity induces changes in the number of transcripts of MGC genes: an increase for TRPC1, TRPC3, TRPM7, TRPP1 (PKD1), TRPP2 (PKD2), TMEM63A, TMEM63B, but a decrease for TRPV2, Piezo1, Piezo2.
View Article and Find Full Text PDFBackground: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca1.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
November 2023
The release of polycyclic aromatic hydrocarbons (PAHs) into the environment due to oil and diesel fuel spills is a serious threat to Arctic fish populations. PAHs produce multiple toxic effects in fish, but disturbance of electrical and contractile activity of the heart seems to be the most negative effect. Our study focused on the effects of fluorene, a tricyclic PAH resembling the well-investigated tricyclic phenanthrene, on major ionic currents and action potential (AP) waveform in isolated ventricular myocytes and on contractile activity in isolated whole hearts of polar navaga cod (Eleginus nawaga).
View Article and Find Full Text PDFVascular smooth muscle voltage-gated potassium (Kv) channels have been proposed to contribute to myogenic autoregulation. Surprisingly, in initial experiments, we observed that the Kv2 channel inhibitor stromatoxin induced vasomotion without affecting myogenic tone. Thus, we tested the hypothesis that Kv2 channels contribute to myogenic autoregulation by fine-tuning the myogenic response.
View Article and Find Full Text PDFTetrahydrocurcumin (THC) is a metabolite of curcumin (CUR). It shares many of CUR's beneficial biological activities in addition to being more water-soluble, chemically stable, and bioavailable compared to CUR. However, its mechanisms of action have not been fully elucidated.
View Article and Find Full Text PDFCurcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs - (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66).
View Article and Find Full Text PDFReactive oxygen species (ROS) and associated oxidative stress are the main contributors to pathophysiological changes following myocardial infarction (MI), which is the principal cause of death from cardiovascular disease. The glutathione (GSH)/glutathione peroxidase (GPx) system appears to be the main and most active cardiac antioxidant mechanism. Hence, enhancement of the myocardial GSH system might have protective effects in the setting of MI.
View Article and Find Full Text PDFThe mechanoelectrical feedback (MEF) mechanism in the heart that plays a significant role in the occurrence of arrhythmias, involves cation flux through cation nonselective stretch-activated channels (SACs). It is well known that nitric oxide (NO) can act as a regulator of MEF. Here we addressed the possibility of SAC's regulation along NO-dependent and NO-independent pathways, as well as the possibility of S-nitrosylation of SACs.
View Article and Find Full Text PDFThe use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways.
View Article and Find Full Text PDFThe main objective of this study was to determine the primary intracellular signalling pathway affected by prolonged (2 hours) incubation in interleukin-2 (IL-2). Based on the inflammatory nature of IL-2, priority was given to the involvement of inhibitory-kappaB kinase/nuclear factor-kappaB (IKK/NF-κB) signalling. All of the experiments were performed on freshly prepared cardiomyocytes isolated from rat left ventricles.
View Article and Find Full Text PDFBackground: This study was undertaken to test the hypothesis that the newly synthesized curcuminoids B2BrBC and C66 supplementation will overcome hyperoxia-induced tracheal hyperreactivity and impairment of relaxation of tracheal smooth muscle (TSM).
Materials And Methods: Rat pups (P5) were exposed to hyperoxia (>95% O ) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10 -10 M) or relaxation induced by electrical field stimulation (5-60 V) in the presence/absence of B2BrBC or C66, or to study the direct relaxant effects elicited by both analogs.
Bull Exp Biol Med
December 2019
The whole-cell patch-clamp technique was used to examine the effect of gadolinium Gd (a non-specific blocker of mechanically gated current I, a component of late current I) on ionic currents in insolated rat ventricular cardiomyocytes alone and in combination with the blockers of L-type calcium currents (I) nifedipine (10 μM) or verapamil (1 μM). In K/K or Cs/Cs media, blockade of I produced no effect on I at negative potentials, but inhibited I at positive ones. In K/K medium, Gd (5 μM) decreased the net persistent current (I) at -45 mV from 198.
View Article and Find Full Text PDFFor 22 days after monocrotaline injection two groups of rats received either of the monocarbonyl curcumin analogs (2E,6E)-2,6-bis(2-bromobenzylidene)cycloxehanone (B2BrBC) and (2E,6E)-2,6-bis([2-trifluoromethyl]benzylidene)cyclohexanone (C66), and their right ventricle parameters were compared to those from the control and the monocrotaline injected animals. B2BrBC and C66 treatments did not prevent the monocrotaline-induced right ventricular hypertrophy but attenuated the changes in antioxidant enzyme activities and reduced inflammation. The level of thiol-based nonenzymatic antioxidants did not change in the function of monocrotaline or curcumin analogs treatment.
View Article and Find Full Text PDFThe purpose of this study was to examine the effects of interferon-γ (IFN-γ) on calcium movement in rat ventricular myocytes. L-type Ca currents (I) were recorded with the whole-cell configuration of the patch-clamp techniques. IFN-γ induces current density reduction at the test potential of 0 mV by 47.
View Article and Find Full Text PDFPurpose: Studies of negative ionotropic effects of IL-2 create the basis for possible IL-2 impact on nonselective conductance (G), which potentially makes these effects useful in elucidation of the pathways affected by IL-2.
Materials And Methods: A culture of human cardiac fibroblasts (CHCFs) was used in this study. A voltage clamp mode of the whole-cell patch-clamp technique was introduced.
Pril (Makedon Akad Nauk Umet Odd Med Nauki)
July 2018
The following study examined the impact of IL-2 on Ca channel activity in the event of several hours' incubation in IL-2. The right ventricle free wall for action potential measurements was isolated and perfused with Tyrode solution. The whole-cell voltage clamp experiments were performed on enzymatically isolated single cardiomyocytes.
View Article and Find Full Text PDFAim: To identify the most significant factor influencing blood levels of cytokines in patients at high and very high cardiovascular risk.
Materials And Methods: A patient base from the "Management of chronic patients with multiple diseases" project was analyzed. 523 patients (mean age, 87±17.
Purpose: The present study investigated the influence of IL-18/18R genetic variants on cytokine expression in patients with stable coronary artery disease (CAD).
Materials And Methods: The polymorphisms rs1946518, rs187238, rs326, rs1169288, and rs183130 were determined in patients with and without CAD. Circulating cytokine levels were measured immunologically.