SOD2 mRNA as a potential biomarker for exercise: interventional and cross-sectional research in healthy subjects.

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono-nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).

Role of HO-1 against Saturated Fatty Acid-Induced Oxidative Stress in Hepatocytes.

Increased circulating levels of free fatty acids, especially saturated ones, are involved in disease progression in the non-alcoholic fatty liver. Although the mechanism of saturated fatty acid-induced toxicity in the liver is not fully understood, oxidative stress may be deeply involved. We examined the effect of increased palmitic acid, the most common saturated fatty acid in the blood, on the liver of BALB/c mice via tail vein injection with palmitate. After 24 h, among several anti-oxidative stress response genes, only heme oxygenase-1 (HO-1) was significantly upregulated in palmitate-injected mice compared with that in vehicle-injected mice. Elevation of HO-1 mRNA was also observed in the fatty liver of high-fat-diet-fed mice. To further investigate the role of HO-1 on palmitic acid-induced oxidative stress, in vitro experiments were performed to expose palmitate to HepG2 cells. SiRNA-mediated knockdown of HO-1 significantly increased the oxidative stress induced by palmitate, whereas pre-treatment with SnCl2, a well-known HO-1 inducer, significantly decreased it. Moreover, SB203580, a selective p38 inhibitor, reduced HO-1 mRNA expression and increased palmitate-induced oxidative stress in HepG2 cells. These results suggest that the HO-1-mediated anti-oxidative stress compensatory reaction plays an essential role against saturated fatty acid-induced lipotoxicity in the liver.

Human albumin augmented airway inflammation induced by PM2.5 in NC/Nga mice.

The synergic allergic inflammatory effects of particulate matter (PM) 2.5 and human albumin were investigated in NC/Nga mice, which are hypersensitive to mite allergens. PM2.5 or PM2.5 plus human albumin with aluminum oxide was injected twice intraperitoneally for sensitization. After 7 days, PM2.5 or PM2.5 plus human albumin was administered five times intranasally to mice for further sensitization. Subsequently, PM2.5 was administered as a challenge on the 11th day. On the 12th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 , Th2 cytokines, chemokines, and mucus proteins (MUC5AC and MUC5B) in the lung tissue and histopathology. Although PM2.5 or human albumin alone did not induce allergic airway inflammation, simultaneous inoculation of PM2.5 and human albumin-induced airway inflammation showing increase in AHR, total BALF cell numbers, mRNA levels of IL-13, eotaxin 1, eotaxin 2, and MUC5AC, and anti-IG against human serum albumin. Inflammation was observed around the bronchus in PM2.5 plus human albumin-induced lungs. These results demonstrate that PM2.5 can induce allergic airway inflammation through the synergistic action with human albumin in NC/Nga mice.