No abstract

We investigated the utility of branched-chain amino acids (BCAA) in dexamethasone-induced muscle atrophy. Dexamethasone (600 microg/kg, intraperitoneally) and/or BCAA (600 mg/kg, orally) were administered for 5 days in rats, and the effect of BCAA on dexamethasone-induced muscle atrophy was evaluated. Dexamethasone decreased total protein concentration of rat soleus muscles. Concomitant administration of BCAA reversed the decrease. Dexamethasone decreased mean cross-sectional area of soleus muscle fibers, which was reversed by BCAA. Dexamethasone increased atrogin-1 expression, which has been reported to play a pivotal role in muscle atrophy. The increased expression of atrogin-1 mRNA was significantly attenuated by BCAA. Furthermore, dexamethasone-induced conversion from microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II, which is an indicator of autophagy, was blocked by BCAA. These findings suggest that BCAA decreased protein breakdown to prevent muscle atrophy. BCAA administration appears to be useful for prevention of steroid myopathy.

No abstract

Prop1 activates POU1F1 (Pit-1) gene expression, which in turn stimulates GH, PRL, TSHbeta and GHRH receptor gene expressions. Therefore the patients with Prop1 mutation show GH, PRL, and TSH deficiency. The mutation of Prop1 is a major abnormality causing combined pituitary hormone deficiency (CPHD). However, DNA-binding and activating functions of mutant Prop1 have not been examined fully because Prop1-binding elements (PBEs) in human POU1F1 gene were not identified until 2008. The aim of this study is to test DNA-binding and transcriptional activities of two mutant Prop1s (W194XProp1 and S156insTProp1, both of them were found in the patients with CPHD) whose mutation is located in putative transactivating domain but not in DNA-binding domain. W194XProp1 showed a marked DNA-binding to PBE as well as a consensus element of paired-like transcription factors (PRDQ9). Activating function for POU1F1 reporter genes expression was lost or decreased in W194XProp1 but still preserved for PRDQ9 reporter gene. S156insTProp1 did not bind PBE but bound PRDQ9. Consistent with the result, S156insTProp1 did not stimulate POU1F1 reporter gene but stimulated PRDQ9 reporter gene. These results support the inference that W194XProp1 is unable to increase POU1F1 gene expression by the defect of transactivating domain and that S156insTProp1 is unable to increase due to the loss of DNA-binding activity. DNA-binding domain that has been assumed is not sufficient to provide full DNA-binding activity of Prop1 and transactivating domain of Prop1 is likely to affect DNA binding to PBE.