Cofilin-1 and profilin-1 expression in lung microvascular endothelial cells exposed to titanium dioxide nanoparticles

An, Min‐Hyeok; Choi, Seon-Muk; Lee, Pureun‐Haneul; Park, Shinhee; Baek, Ae-Rin; Jang, An‐Soo

doi:10.17219/acem/152032

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…These findings identified cofilin2 phosphorylation and F-actin disassembly as novel downstream effectors of DNA-PKcs activation in endotoxemia-induced endothelial injury, thus elucidating the molecular basis by which LPS promotes endothelial cytoskeleton degradation. Most previous studies focused on the impact of cofilin1 phosphorylation on endothelial dysfunction during physiopathological and toxicological conditions [ 55 – 57 ]. Cofilin1 is mainly expressed in nonmuscle tissue, while cofilin2 is abundant in muscle [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy

Du,

Zhu,

et al. 2024

Research

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The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr 25 . Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2 Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.

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Section: Discussionmentioning

confidence: 99%

DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy

Du,

Zhu,

et al. 2024

Research

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“…Our previous studies showed that a long-term (for 1 and 3 months) intragastric intake of nano-TiО 2 by rats leads to its selective accumulation in tissues and organs, and is accompanied by changes in the motility of visceral SMs (Tsymbalyuk et al, 2017;Tsymbalyuk et al, 2019;An et al, 2022) Since nanoparticles are known to enter the tissues of the digestive tract wall and partially accumulate there, studying the state of the pacemaker mechanisms of regulation of smooth muscle spontaneous contractions in the stomach and large intestine under chronic exposure to TiО 2 nanoparticles is relevant and interesting. Thus the aim of this research work was to study the spontaneous contractile activity of the gastric and large intestine SMs of rats under chronic (for 6 months) intake of an aqueous suspension of TiО 2 nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Mechanokinetics of the spontaneous contractions of smooth muscles in the stomach and large intestine of rats under chronic effect of ТiО2 nanoparticles

et al. 2023

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Background. Currently, nano-sized materials of titanium dioxide (TiО2) have wide industrial uses, particularly in the food industry and pharmacology. Therefore, the problem of TiО2 toxicity to living organisms in case of their chronic in vivo intake needs thorough investigation. As nanoparticles enter the internal environment of the body, they spread with the bloodstream to tissues and organs, where they partially accumulate. Thus studying the state of the pacemaker mechanisms of regulation of smooth muscle spontaneous contractions in the stomach and large intestine under chronic exposure to TiО2 nanoparticles is relevant and interesting. The purpose of this research work was to study the spontaneous contractile activity of the gastric and large intestine smooth muscles of rats under chronic (for 6 months) intake of an aqueous suspension of TiО2 nanoparticles. Materials and Methods. Wistar rats were used in the experiments. Rats of the experimental group were daily intragastrically administered an aqueous suspension of ТіО2 nanoparticles for six months at a dose of 0.1 mg/kg. The study of the mechanokinetics of the contraction-relaxation process of muscle preparations was carried out according to the method (Kosterin et al., 2021) with the calculation of the mechanokinetic parameters of the contraction-relaxation cycle: force (Fmax, FC and FR), time (τ0, τC and τR), impulse (Іmax, ІC and ІR) and velocity (VC and VR). Results. A comprehensive mechanokinetic analysis of spontaneous contractions of the antrum and caecum circular smooth muscles was carried out in control and under chronic in vivo exposure to ТіО2 nanocolloids (0.1 mg/kg/day) for 6 months. It was found that the chronic action of ТіО2 nanocolloids significantly inhibits the contractile activity of the antrum smooth muscles accompanied by a decrease in all mechanokinetic parameters of time, force, velocity and impulse. Under the same conditions, inhibition of the spontaneous contractions of the large intestine smooth muscles was observed. However, the time (τ0, τC and τR) and impulse (Іmax, ІC and ІR) parameters increased for these muscles against the background of the decrease in the force and velocity mechanokinetic parameters. Conclusions. Modulation of the mechanokinetic parameters of the spontaneous contractile activity of the stomach and large intestine smooth muscles of rats under chronic intragastric administration of ТіО2 nanocolloids suggests that the functioning of pacemakers changes significantly under these conditions. Since the parameters of the contraction and relaxation phases of both the stomach and the large intestine smooth muscles do not differ by the magnitude of the inhibitory effects, it can be assumed that the effects of ТіО2 are not specific for particular Са2+ transport systems involved in contractile responses.

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The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles

Tian,

Pang,

et al. 2024

Ecotoxicology and Environmental Safety

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Cofilin-1 and profilin-1 expression in lung microvascular endothelial cells exposed to titanium dioxide nanoparticles

Abstract: and profilin-1 expression in lung microvascular endothelial cells exposed to titanium dioxide nanoparticles [published online as ahead of print on August 24, 2022].

Cited by 3 publications

References 43 publications

DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy

DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy

Mechanokinetics of the spontaneous contractions of smooth muscles in the stomach and large intestine of rats under chronic effect of ТiО2 nanoparticles

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles

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