The role of mitochondrial KATP channel in anti-inflammatory effects of uridine in endotoxemic mice

Mironova, Galina D.; Хренов, М. О.; Talanov, Eugeny Yu.; Глушкова, О. В.; Parfenyuk, Svetlana B.; Новоселова, Т. В.; Лунин, С. М.; Belosludtseva, Natalia V.; Новоселова, Е. Г.; Lemasters, John J.

doi:10.1016/j.abb.2018.07.006

Cited by 26 publications

(26 citation statements)

References 29 publications

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“…It is known that the administration of uridine increases the concentration of UDP in tissues. The intraperitoneal injection of uridine (30 mg/kg) to rats was found to increase UDP approximately two times after 30–60 min in spleen and heart tissues 22 , which is sufficient for the channel activation, since the effective UDP concentration is 20 μM 13,23 . This suggestion was confirmed by the experiments with 5-HD, a selective inhibitor of mitoK ATP 24,25 .…”

Section: Discussionmentioning

confidence: 98%

Uridine as a protector against hypoxia-induced lung injury

Rozova

Mankovskaya

Belosludtseva

et al. 2019

Sci Rep

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The effect of the activation of the mitochondrial ATP-dependent potassium channel (mitoK ATP ) on the ultrastructure of rat lung in acute hypoxic hypoxia (7% of oxygen in nitrogen, exposure 30 min) was studied. It was shown that uridine, a precursor of the mitoK ATP activator UDP, exerted a protective effect against hypoxic damage to the lung. The administration of uridine to animals prior to hypoxia decreased the number of mitochondria with altered ultrastructure and prevented the hypoxia-induced mitochondrial swelling. Uridine also protected the epithelial, interstitial and endothelial layers of the air–blood barrier from the hypoxia-induced hyperhydration. The protective action of uridine against hypoxia-induced lung injury was eliminated by the selective blocker of mitoK ATP 5-hydroxydecanoate. These data suggest that one of the mechanisms of the positive effect of uridine is related to the activation of the mitoK ATP channel, which, according to the literature and our data, is involved in the protection of tissues from hypoxia and leads to adaptation to it. A possible role of uridine in the maintenance of the mitochondrial structure upon hypoxia-induced lung injury and the optimization of oxygen supply of the organism is discussed.

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Section: Discussionmentioning

confidence: 98%

Uridine as a protector against hypoxia-induced lung injury

Rozova

Mankovskaya

Belosludtseva

et al. 2019

Sci Rep

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“…Uridine is a glycosylated uracil that plays a role in synthesis of glycolipids and glycoproteins, DNA and RNA ( Deng et al., 2017 ). As a precursor of uridine triphosphate (UTP), uridine is able to stimulate the synthesis of glycogen ( Mironova et al., 2018 ). Long term uridine supplementation has been shown to enhance lipid accumulation in the liver, and increase glucose levels in blood during fasting in mice ( Urasaki et al., 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts

Gerou

Hall

Woof

et al. 2021

Neurobiology of Aging

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Highlights Aging affects the metabolic profile of fibroblasts derived from ALS cases Increased NADH metabolism with age is observed in the presence of a specific set of catabolic energy substrates in healthy individuals Reduced NADH metabolism with age is observed in the presence of glycogen in the ALS cohort Disease progression rates in ALS cases correlate with fibroblast NADH production in the presence of a number of energy substrates including inosine

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“…IL‐6 and IL‐8 are beneficial in the enhancement of the expression of pro‐inflammatory cytokines and the differentiation of epithelial cells before birth . Recently, it has been found that UR could be used as a drug in the treatment of excessive inflammation . IL‐10 has also been shown to play a vital role in the regulation of intestinal epithelial integrity and suppressing the release of many pro‐inflammatory cytokines and chemokines, including TNF‐ α , IL‐1, IL‐6 and IL‐8 .…”

Section: Discussionmentioning

confidence: 98%

“…50 Recently, it has been found that UR could be used as a drug in the treatment of excessive inflammation. 51 IL-10 has also been shown to play a vital role in the regulation of intestinal epithelial integrity and suppressing the release of many proinflammatory cytokines and chemokines, including TNF-⊍, IL-1, IL-6 and IL-8. 52 The observed upregulation of IL-6 and IL-8 in the UR group suggests that the supplementation of UR may play important roles in regulating inflammation in piglets during late pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Maternal dietary uridine supplementation reduces diarrhea incidence in piglets by regulating the intestinal mucosal barrier and cytokine profiles

Gao

Liu

et al. 2020

J Sci Food Agric

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BACKGROUND Nucleotides play an important role in the regulation of cellular energy and protein homeostasis, which facilitate the repair, recovery and repletion of tissue function. This study tested the effects of maternal uridine (UR) supplementation during late pregnancy and lactation of sows on the immune function of the small intestine in neonatal and suckling piglets. RESULTS Results showed that compared to the control group, maternal dietary UR supplementation significantly decreased incidence of diarrhea in suckling piglets (P < 0.01); and increased both duodenal and ileal average villus height (P < 0.01) as well as villus height/crypt depth in ileum (P = 0.017) in neonatal piglets. RT‐qPCR results showed that maternal UR supplementation decreased mRNA expression of claudin‐1 in jejunum and ileum of neonatal piglets (P < 0.05), while significantly increased mRNA expression of claudin‐1 in duodenum and jejunum of suckling piglets. Furthermore, in suckling piglets, maternal dietary UR supplementation increased mRNA expression of IL‐6, IL‐8 and IL‐1β in duodenum, jejunum and ileum (P < 0.05), increased IL‐10 expression in both jejunal and ileal mucosa (P < 0.05) and increased mRNA expression of IKB and TLR4 in ileal mucosa (P < 0.05). CONCLUSIONS These results suggest that maternal dietary supplementation with UR contributed to reducing incidence of diarrhea by regulating cytokine secretion and intestinal mucosal barrier function in suckling piglets. © 2020 Society of Chemical Industry

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The role of mitochondrial KATP channel in anti-inflammatory effects of uridine in endotoxemic mice

Cited by 26 publications

References 29 publications

Uridine as a protector against hypoxia-induced lung injury

Uridine as a protector against hypoxia-induced lung injury

Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts

Maternal dietary uridine supplementation reduces diarrhea incidence in piglets by regulating the intestinal mucosal barrier and cytokine profiles

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