L-malate, a tricarboxylic acid cycle (TCA ) intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production and may be involved in the beneficial effects of improving physical stamina. In the present study, we investigated the effects of L-malate on the performance of forced swimming time and blood biochemical parameters related to fatigue – blood urea nitrogen (BUN), glucose (Glc), creatine kinase (CK) , total protein (TP) and lactic acid (LA). To investigate the effects of L-malate on the malate-aspartate shuttle and energy metabolism in mice, the activities of enzymes related to the malate-aspartate shuttle were measured. L-malate was orally administered to mice continuously for 30 days using a feeding atraumatic needle. The swimming time was increased by 26.1 % and 28.5 %, respectively, in the 0.210 g/kg and 0.630 g/kg L-malate-treated group compared with the control group. There were no differences in the concentrations of Glc, BUN and TP between the L-malate-treated groups and the control groups. However, the levels of CK were significantly decreased in the L-malate-treated groups. The results predict a potential benefit of L-malate for improving physical stamina and minimizing muscle damage during swimming exercise. The activities of cytosolic and mitochondrial malate dehydrogenase were significantly elevated in the L-malate-treated group compared with the control group. These enzymatic activities may be useful indicators for evaluating changes affecting the malate-aspartate shuttle and energy metabolism in the liver of mice., J. L. Wu, Q. P. Wu, J. M. Huang, R. Chen, M. Cai, J. B. Tan., and Obsahuje bibliografii a bibliografické odkazy
Abnormal accumulation of lymphoblasts in the blood and bone marrow is the main characteristic of acute lymphoblastic leukaemia (ALL). Glucocorticoids are effective drugs for ALL, while glucocorticoid resistance is an obstacle to ALL therapy. MicroRNAs (miRNAs) are implicated in the drug resistance and modulate the response of ALL to glucocorticoids. The role of miR-503 in glucocorticoid sensitivity of ALL was investigated in this study. Firstly, T-leukaemic cells were isolated from patients with ALL. The human ALL cell line (CCRF/CEM) was incubated with dexamethasone to establish a glucocorticoid- resistant ALL cell line (CCRF/CEM-R). Data from MTT showed that IC50 (50% inhibitory concentration) of dexamethasone in T-leukaemic cells isolated from glucocorticoid-resistant ALL patients or CCRF/CEM-R was increased compared with IC50 in T-leukaemic cells isolated from glucocorticoid- sensitive ALL patients or CCRF/CEM. MiR- 503 was down-regulated in glucocorticoid-resistant leukaemic cells and CCRF/CEM-R. Secondly, overexpression of miR-503 sensitized CCRF/CEM-R to dexamethasone. Moreover, over-expression of miR- 503 also promoted the sensitivity of ALL cells to dexamethasone. Thirdly, miR-503 bound to WNT3A mRNA and negatively regulated the expression of WNT3A. Over-expression of miR-503 reduced protein expression of nuclear β-catenin, and over-expression of WNT3A attenuated the miR-503 overexpression- induced decrease in nuclear β-catenin. Lastly, the over-expression of miR-503-induced increased sensitivity of ALL-resistant cells and CCRF/ CEM-R to dexamethasone was attenuated by overexpression of WNT3A. In conclusion, miR-503 targeted WNT3A mRNA to sensitize ALL cells to glucocorticoids through inactivation of the Wnt/β-catenin pathway.