Human SOD2 peptide

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2(+/-)) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1 beta elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Purpose To examine the relationship between changes in nuclear factor erythroid 2-related factor 2 (Nrf2) expression and markers of mitochondrial biogenesis in acutely and chronically exercised human skeletal muscle. Methods The impact of acute submaximal endurance (END) and supramaximal interval (Tabata) cycling on the upregulation of Nrf2 (and its downstream targets), nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) mRNA expression was examined in healthy young males (n = 10). The relationship between changes in citrate synthase (CS) maximal activity and the protein content of Nrf2, heme oxygenase 1 (HO-1), NRF-1, and TFAM was also investigated following 4 weeks of Tabata in a separate group of males (n = 21). Results Nrf2, NRF-1, and HO-1 mRNA expression increased after acute exercise (p < 0.05), whereas the increase in superoxide dismutase 2 (SOD2) mRNA expression approached significance (p = 0.08). Four weeks of Tabata increased CS activity and Nrf2, NRF-1, and TFAM protein content (p < 0.05), but decreased HO-1 protein content (p < 0.05). Training-induced changes in Nrf2 protein were strongly correlated with NRF-1 (r = 0.63, p < 0.01). When comparing protein content changes between individuals with the largest (HI: + 23%) and smallest (LO: - 1%) observed changes in CS activity (n = 8 each), increases in Nrf2 and TFAM protein content were apparent in the HI group only (p < 0.02) with medium-to-large effect sizes for between-group differences in changes in Nrf2 (eta(2)(p)(=)0.15) and TFAM (eta(2)(p) = 0.12) protein content. Conclusion Altogether, our findings support a potential role for Nrf2 in exercise-induced mitochondrial biogenesis in human skeletal muscle.