Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats

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We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague–Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (..) (AU)

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats.

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague-Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (DEG; n = 8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). The levels of t-PI3-K, p-PI3-K, and p-CREB, and the p-CREB/t-CREB ratio significantly increased in the NEG (p < 0.001, respectively). The p-PI3-K/t-PI3-K ratio significantly increased in the DEG (p < 0.001). The p-Erk1/t-Erk1 ratio significantly increased in the NEG (p < 0.001), whereas the p-Erk2/t-Erk2 ratio significantly decreased in the DCG and DEG (p < 0.001). The caspase-3 level significantly increased in the DCG compared with that in the DEG (p < 0.001). These results suggest that treadmill exercise increases NGF levels and accelerates p-PI3-K activation in order to suppress apoptotic cell death in the soleus muscle of diabetic rats.

Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats.

While nerve growth factor (NGF) activates various signaling cascades, the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway plays a pivotal role in controlling the survival of neurons, although this activity declines during the aging process. We investigated the effect of forced moderate-intensity treadmill exercise on the level of NGF and the PI3-K/Akt signaling pathway in the hippocampus of induced aging rats. Forty-five male Sprague-Dawley rats were divided into the following three groups: (1) control group, in which aging was not induced (CON: n=15), (2) aging-control group, in which aging was induced but the rats were not subjected to exercise (ACON: n=15), and (3) the aging-exercise group, in which aging was induced and the rats were subjected to treadmill exercise (AEX: n=15). d-Galactose (50mg/kg) was injected into the abdominal cavity for 8 weeks to induce aging. Rats were subjected to treadmill exercise 5 days a week for 8 weeks, and the speed of the treadmill was gradually increased. The protein levels of NGF, P-PI3-K, and P-Akt were significantly high in the AEX group (p<0.01, p<0.01, and p<0.001, respectively). Tyrosine kinase A (Trk A) receptor level was significantly higher in the CON and AEX groups than in the ACON group (p<0.01). TUNEL assay showed a significant reduction in apoptosis in the AEX group (p<0.001). Caspase-3 activation was significantly decreased in the AEX and CON groups (p<0.05). These results show that forced moderate-intensity treadmill exercise increases the level of NGF and activates P-PI3-K to induce P-Akt in order to suppress apoptotic cell death in the hippocampus of induced aging rats.

The combination of alpha-lipoic acid supplementation and aerobic exercise inhibits lipid peroxidation in rat skeletal muscles.

We investigated the effect of DL-alpha-lipoic acid (LA) supplementation and regular aerobic exercise on the concentrations of malondialdehyde (MDA) and vitamin E, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the levels of glutathione (GSH) in rat skeletal muscles (soleus and red gastrocnemius). For 8 weeks, rats (n = 7 per group) were (1) exercised on a treadmill for 30 min d(-1), (2) treated with supplemental LA, or (3) exercised and treated with supplemental LA. Control rats (n = 7) did not receive LA and were not exercised. DL-alpha-lipoic acid (100 mg kg(-1)) was administered daily as an oral supplement. The rats were exercised in a graded manner for 5 d wk(-1). The concentration of MDA in the soleus and red gastrocnemius was significantly lower in rats that exercised and received LA than in the other groups. Compared with the other groups, rats that exercised and received LA had a significantly higher vitamin E concentration in the soleus. The SOD and GPx activities in the soleus and red gastrocnemius were significantly higher in rats that exercised and received LA. These results suggest that LA supplementation combined with aerobic treadmill exercise inhibits lipid peroxidation in skeletal muscles. This effect was especially remarkable in the soleus, which is particularly sensitive to oxidative stress, as revealed by the increased vitamin E level and SOD and GPx activities.