1. Myo-inositol oxygenase (MIOX) accelerated inflammation in the model of infection-induced cardiac dysfunction by NLRP3 inflammasome.
- Author
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Zhou W, Yu C, and Long Y
- Subjects
- Animals, Male, Mice, Inflammasomes metabolism, Inflammation, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, RNA, Messenger, Humans, Heart Diseases, Inositol Oxygenase metabolism, Sepsis complications
- Abstract
Background: Cardiac dysfunction is an important component of multiple organ failure caused by sepsis, and an important cause of high mortality in patients with sepsis. Herein, we attempted to determine whether myo-inositol oxygenase (MIOX) has proinflammation enzyme in infection-induced cardiac dysfunction (IICD) and its underlying mechanism., Methods: Patients with IICD were collected by our hospital. A mouse model of IICD was induced into male db/db mice by cecal ligation and puncture (CLP). All mice were injected with 20 μL of LV-MIOX or LV-control short hairpin RNA using a 0.5-mL insulin syringe. On the second day, all mice were induced by CLP. H9C2 cell was also induced with lipopolysaccharide and adenosine triphosphate. Quantitative analysis of messenger RNAs (mRNAs) and gene microarray hybridization was used to analyze the mRNA expression levels. Enzyme-linked immunosorbent assay, immunofluorescence, and Western blot analysis were used to analyze the protein expression levels., Results: The serum expressions of MIOX mRNA level in patients with IICD were upregulated compared to normal healthy volunteers. MIOX promoted inflammation levels in the in vitro model of IICD. Si-MIOX inhibited inflammation levels in the in vitro model of IICD. MIOX accelerated inflammation and cardiac dysfunction in infection-induced mice. MIOX interacted with NLR family pyrin domain containing 3 (NLRP3) protein to reduce the degradation of NLRP3. The inhibition of MIOX reversed the effects of NLRP3 in the in vitro model of cardiac dysfunction., Conclusions: Taken together, these findings demonstrate that MIOX accelerates inflammation in the model of IICD, which may be, at least in part, attributable to NLRP3 activity by the suppression of NLRP3 degradation in IICD., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)
- Published
- 2023
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