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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 (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.

The present study was undertaken to further investigate the protective effect of treadmill exercise on the hippocampal proteins associated with neuronal cell death in an aged transgenic (Tg) mice with Alzheimer's disease (AD). To address this, Tg mouse model of AD, Tg-NSE/PS2m, which expresses human mutant PS2 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. The exercised mice were treadmill run at speed of 12 m/min, 60 min/day, 5 days/week on a 0% gradient for 3 months. Treadmill exercised mice improved cognitive function in water maze test. Treadmill exercised mice significantly reduced the expression of Aβ-42, Cox-2, and caspase-3 in the hippocampus. In parallel, treadmill exercised Tg mice decreased the phosphorylation levels of JNK, p38MAPK and tau (Ser404, Ser202, Thr231), and increased the phosphorylation levels of ERK, PI3K, Akt and GSK-3α/β. In addition, treadmill exercised Tg mice up-regulated the expressions of NGF, BDNF and phospho-CREB, and the expressions of SOD-1, SOD-2 and HSP-70. Treadmill exercised Tg mice up-regulated the expression of Bcl-2, and down-regulated the expressions of cytochrome c and Bax in the hippocampus. The number of TUNEL-positive cells in the hippocampus in mice was significantly decreased after treadmill exercise. Finally, serum TC, insulin, glucose, and corticosterone levels were significantly decreased in the Tg mice after treadmill exercise. As a consequence of such change, Aβ-dependent neuronal cell death in the hippocampus of Tg mice was markedly suppressed following treadmill exercise. These results strongly suggest that treadmill exercise provides a therapeutic potential to inhibit both Aβ-42 and neuronal death pathways. Therefore, treadmill exercise may be beneficial in prevention or treatment of AD., (Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

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.

Background: Whether vitamin D deficiency is related to rotator cuff muscle and tendon physiology is controversial. Purpose: To assess the relationship between vitamin D deficiency and various gene expression patterns in patients with rotator cuff tears. Study Design: Controlled laboratory study. Methods: During arthroscopic surgery, samples from the supraspinatus muscle, deltoid muscle, and supraspinatus tendon were acquired from 12 patients with vitamin D deficiency (serum 25-hydroxyvitamin D concentration <20 ng/dL) and 12 patients with sufficient vitamin D levels (control group, serum 25-hydroxyvitamin D concentration ≥30 ng/dL) who were matched for age, sex, and tear size. Alterations in the expression of genes and proteins associated with myogenesis, muscle atrophy, adipogenesis, inflammation, and apoptosis, as well as in vitamin D receptor expression, were assessed using quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry and were compared between the 2 groups. Results: Vitamin D receptor gene expression in the deltoid muscle was significantly lower in the vitamin D deficiency group than in the control group (P =.043). Additionally, in the deltoid muscle, myoDgene expression levels were lower and atrogin levels were higher in the vitamin D deficiency group than in the control group (P =.034 and P =.011, respectively). However, in the supraspinatus muscle, no differences were observed between groups in the expression of myogenesis- or atrophy-related genes (all P >.05). The expression of inflammation-related genes (interleukin (IL)-1β and IL-6) was significantly higher in the vitamin D deficiency group, in both the deltoid and supraspinatus muscles (all P <.05). The supraspinatus tendon tissue did not show any significant differences in any gene expression evaluated (all P >.05). A correlation between gene and protein expression was observed for atrogin and IL-1β in the deltoid muscle (P =.019 and P =.037, respectively) and for IL-6 in the supraspinatus muscle (P =.044). Conclusion: Vitamin D deficiency was not associated with the expression of myogenesis-related or muscle atrophy–related genes in the supraspinatus muscle of patients with rotator cuff tears, unlike in the deltoid muscle; rather, vitamin D deficiency was associated with increased proinflammatory cytokine expression. Clinical Relevance: In patients with rotator cuff tears, vitamin D deficiency was observed to be associated with increased levels of proinflammatory cytokines in the rotator cuff muscles, without significant changes in gene expression related to myogenesis or muscle atrophy. [ABSTRACT FROM AUTHOR]

Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer. [ABSTRACT FROM AUTHOR]