C60 fullerenes selectively inhibit BKCa but not Kv channels in pulmonary artery smooth muscle cells

Melnyk, Mariia I.; Ivanova, Irina; Dryn, Dariia O.; Prylutskyy, Yuriy; Hurmach, Vasyl V.; Платонов, М. О.; Kury, Lina T. Al; Ritter, Uwe; Soloviev, Anatoly I.; Zholos, Alexander

doi:10.1016/j.nano.2019.03.018

Cited by 16 publications

(12 citation statements)

References 55 publications

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“…It is known that the size of C 60 fullerene particles in aqueous solution strongly correlates with their specific biological properties and toxicity. So, the antibacterial activity of C 60 fullerene is connected with its ability to undergo aggregation [ 21 ]; the macrophage apoptosis induced by aqueous C 60 fullerene aggregates changes the mitochondrial membrane potential [ 22 ]; the respiratory toxicity and immunotoxicity of C 60 fullerenes in mice and rats after nose inhalation strictly depends on their nano- and micro-size [ 23 ]; depending on the size C 60 fullerenes can inhibit BK Ca but not K v channels in pulmonary artery smooth muscle cells [ 24 ], penetrate through plasma membrane inside the cell [ 25 ] or be adsorbed on the surface of the membrane [ 26 ]. Therefore, the size effect of C 60 fullerene particles in aqueous solution is considered now to be very important.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene

Nozdrenko

Абрамчук

Prylutska

et al. 2021

IJMS

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The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 μg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40–45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55–65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.

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Section: Resultsmentioning

confidence: 99%

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene

Nozdrenko

Абрамчук

Prylutska

et al. 2021

IJMS

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“…Due to this distribution of calcium-activated potassium channels, one previous study have shown that the vasodilation of EDHF was attenuated by NO synthase inhibition in the pulmonary artery of rats [18], while another studies have reported that the vasodilation effect of EDHF continues significantly in the presence of the combination of L-NAME and the cyclooxygenase inhibitor indomethacin [19]. One recent study supported that after inhibition BKCa, phenylephrine-induced contraction of pulmonary artery rings enhanced about 25% [20].…”

Section: Discussionmentioning

confidence: 98%

Opposing responses of the rat pulmonary artery and vein to phenylephrine and other agents in vitro

et al. 2021

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Background Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted pulmonary veins. Through comparing differences in the effects of commonly used vasoactive drugs on pulmonary artery and veins, the study aimed to improve efficiency and accuracy of isolated pulmonary vascular experiments, and to provide experimental basis for clinical drug use. Methods The contractile responses of pulmonary arteries and veins from twelve-week-old Male Sprague-Dawley rats to phenylephrine, arginine vasopressin (AVP), U46619, endothelin-1, and potassium chloride (KCl) were recorded, as well as the relaxation in response to phenylephrine, AVP, acetylcholine. To further explore the mechanism, some vessels was also pre-incubated with adrenergic receptors antagonists propranolol, prazosin and nitric oxide synthesis inhibitor N[gamma]-nitro-L-arginine methyl ester (L-NAME) before addition of the experimental drugs. Results Phenylephrine constricted pulmonary veins directly, but constricted pulmonary artery only after incubation with propranolol or/and L-NAME. The pulmonary artery exhibited significant relaxation to AVP with or without L-NAME incubation. AVP more clearly constricted the veins after incubation with L-NAME. Changes in vascular tension also varied from pulmonary artery to veins for KCl stimulation. Different from phenomena presented in veins, acetylcholine did not relax pulmonary artery preconstricted by KCl, U46619, and endothelin-1. Conclusions According to the results, phenylephrine, KCl, AVP, and acetylcholine could be used to distinguish pulmonary arteries and pulmonary veins in vitro. This also suggested that the pulmonary arteries and pulmonary veins have great differences in physiology and drug reactivity.

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“…Molecular docking is among the most frequently used numerical techniques, due to its ability to predict the binding-conformation of small molecule ligands to the appropriate target binding site [49]. MD simulation is also one of the most frequently used techniques to evaluate the stability of the "ligand-protein (target)" molecular system [23,50].…”

Section: Modeling Of Swcnt Binding To Trpc4 Channelmentioning

confidence: 99%

“…We have previously characterized C 60 fullerenes as novel inhibitors of large-conductance Ca 2+ -activated K + channels in pulmonary artery myocytes [23] and the muscarinic receptor cation current, termed mI CAT , in ileal smooth muscle cells [24]. The latter current is mediated by both TRPC4 and TRPC6 proteins, with TRPC4 acting as its main molecular component [25].…”

Section: Introductionmentioning

confidence: 99%

Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes

et al. 2021

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Single-walled carbon nanotubes (SWCNTs) are characterized by a combination of rather unique physical and chemical properties, which makes them interesting biocompatible nanostructured materials for various applications, including in the biomedical field. SWCNTs are not inert carriers of drug molecules, as they may interact with various biological macromolecules, including ion channels. To investigate the mechanisms of the inhibitory effects of SWCNTs on the muscarinic receptor cation current (mICAT), induced by intracellular GTPγs (200 μM), in isolated mouse ileal myocytes, we have used the patch-clamp method in the whole-cell configuration. Here, we use molecular docking/molecular dynamics simulations and direct patch-clamp recordings of whole-cell currents to show that SWCNTs, purified and functionalized by carboxylation in water suspension containing single SWCNTs with a diameter of 0.5–1.5 nm, can inhibit mICAT, which is mainly carried by TRPC4 cation channels in ileal smooth muscle cells, and is the main regulator of cholinergic excitation–contraction coupling in the small intestinal tract. This inhibition was voltage-independent and associated with a shortening of the mean open time of the channel. These results suggest that SWCNTs cause a direct blockage of the TRPC4 channel and may represent a novel class of TRPC4 modulators.

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C60 fullerenes selectively inhibit BKCa but not Kv channels in pulmonary artery smooth muscle cells

Cited by 16 publications

References 55 publications

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene

Opposing responses of the rat pulmonary artery and vein to phenylephrine and other agents in vitro

Single-Walled Carbon Nanotubes Inhibit TRPC4-Mediated Muscarinic Cation Current in Mouse Ileal Myocytes

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