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Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide?induced acute pneumonia in rats.

ABSTRACT: Pneumonia is one of the commonest causes of death worldwide. High?temperature requirement A2 (HtrA2) is a proapoptotic mitochondrial serine protease involved in caspase?dependent or caspase?independent cell apoptosis. UCF?101 (5?[5?(2?nitrophenyl) furfuryl iodine]?1,3?diphenyl?2?thiobarbituric acid), an inhibitor of HtrA2, has a protective effect on organs in various diseases by inhibiting cell apoptosis. The aim of the present study was to explore whether UCF?101 has a protective effect on lungs in pneumonia. A lipopolysaccharide (LPS)?induced pneumonia model was established in rats. UCF?101 (2 µmol/kg) was used for treatment. Lung injury was detected by hematoxylin and eosin staining. Pro?inflammatory cytokines and oxidative stress?related factors were detected using corresponding test kits. TUNEL staining was used to measure the amount of cell apoptosis. Apoptosis?associated proteins were detected by western blot assay. The present study indicated pulmonary injury induced by LPS. Treatment with UCF?101 clearly alleviated this pulmonary damage and restored the levels of pro?inflammatory cytokines and oxidative stress?related factors. In addition, UCF?101 significantly reduced LPS?induced cell apoptosis, the release of HtrA2 and cytochrome from mitochondria to the cytoplasm and inhibited the expression of pro?apoptotic proteins. UCF?101 also restored the ATP level. The present results demonstrated that UCF?101 acts as a positive regulator of acute pneumonia by inhibiting inflammatory response, oxidative stress and mitochondrial apoptosis. The present study suggests UCF?101 as a potential candidate for pneumonia therapy.

SUBMITTER: Wang X

PROVIDER: S-EPMC7453584 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide‑induced acute pneumonia in rats.

Wang Xin X

Molecular medicine reports 20200804 4

Pneumonia is one of the commonest causes of death worldwide. High‑temperature requirement A2 (HtrA2) is a proapoptotic mitochondrial serine protease involved in caspase‑dependent or caspase‑independent cell apoptosis. UCF‑101 (5‑[5‑(2‑nitrophenyl) furfuryl iodine]‑1,3‑diphenyl‑2‑thiobarbituric acid), an inhibitor of HtrA2, has a protective effect on organs in various diseases by inhibiting cell apoptosis. The aim of the present study was to explore whether UCF‑101 has a protective effect on lung ...[more]

PMID: 32945404

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Project description:BackgroundMale fertility can be hampered by systemic and testicular infections and inflammation, which can lead to impaired spermatogenesis that often cannot be reversed by antibiotic treatment. There has been some suggestion that lycopene (LYC) may be useful in the preservation of fertility, although its mechanisms are complex. This current study examined the therapeutic efficacy of LYC on testicular damage and its underlying mechanisms.MethodsLipopolysaccharide (LPS; 5 mg/kg) was injected intraperitoneally to induce inflammation of the testes in mature male rats. The rats in the experimental group were administered 5 mg/kg LYC intragastrically for 4 weeks. The testes were harvested from the euthanized rats for lipidomics, RNA sequencing, and related experimental tests.ResultsLaboratory data suggested that LPS-induced systemic inflammation induced cytokine excess and oxidative stress in the testes. Administration of oral LYC inhibited the excess cytokine production and oxidative stress, mitigating damage to the testes. Lipidomic studies identified significant changes to 258 lipids and 5 metabolism pathways. Coupled with RNA sequencing analysis, 1,116 genes were found to be significantly regulated and many lipid metabolism-related signaling pathways were identified. The expression of retinoid X receptor alpha (RXR) in the peroxisome proliferator-activated receptor (PPAR) signaling pathway was significantly upregulated after LYC treatment, which activated the RXR/PPAR easy dimer. The expression of downstream genes such as fatty acid binding protein 3 (FABP3) and carnitine palmitoyltransferase 1A (CPT1A) was increased. These genes are involved in the control of fatty acid metabolism, fatty acid degradation, fatty acid chain elongation, and lipid metabolism, which partially explains the changes in the content and composition of lipids.ConclusionsLYC regulates the lipid metabolism of testes and lipid metabolism-related signaling pathways, such as the PPAR signaling pathway. Furthermore, LYC ameliorated the LPS-induced dysregulation of lipid metabolism in the testes, as well as the LPS-induced inflammatory response. This study offers a new perspective for the investigation of the mechanisms in inflammatory testicular damage and potential therapeutic targets.

Dataset Information

Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide?induced acute pneumonia in rats.

Publications

Inhibition of HtrA2 alleviates inflammatory response and cell apoptosis in lipopolysaccharide‑induced acute pneumonia in rats.

Similar Datasets

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