Involvement of inhibitory PAS domain protein in neuronal cell death in Parkinson's disease.

Inhibitory PAS domain protein (IPAS), a repressor of hypoxia-inducible factor-dependent transcription under hypoxia, was found to exert pro-apoptotic activity in oxidative stress-induced cell death. However, physiological and pathological processes associated with this activity are not known. Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. Activation of the PINK1-Parkin pathway attenuated IPAS-dependent apoptosis. IPAS was markedly induced in the midbrain following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and IPAS-deficient mice showed resistance to MPTP-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A significant increase in IPAS expression was found in SNpc neurons in patients with sporadic PD. These results indicate a mechanism of neurodegeneration in PD.

Gender differences in muscle strength after 20 days bed rest.

In the previous studies, when Bed rest (BR) was prolonged over 2 weeks, muscle mass and strength began progressively to become reduced. There are many publications investigating the changes in skeletal muscles during inactivity. However it is still unclear whether the changing degrees of muscle mass and strength not only in antigravity muscles but also in non-antigravity muscles differ between males and females. So, the purpose of this study is to investigate gender difference in the effect of 20 days of BR (BR 20) on regional muscle mass and strength of the arm and leg.

Water intake and urinary volume during 20 days bed-rest in young woman.

During the bed-rest in the young subjects, the water intake should be depressed, because the diuretic is probably accelerated, and then the total body water and body weight is decreased by the water loss. In our previous study in 1991, we have reported that urinary volume was gradually increased, while water intake was decreased. Therefore, it was concluded that the decrease in the water intake and the increase in the urinary volume should bring to the negative water balance. In the present study, it is studied whether urinary volume is independent on water intake during 20 days horizontal bed-rest in young woman.

Effects of 20 days bed-rest on cardio respiratory functions during sub-maximal exercise in young woman.

The purpose of present study is to know the effects of 20 days bed-rest on cardio-respiratory functions during sub-maximal exercise in different body positions which were in sitting, supine and 30 degrees head-down position respectively.

Effects of 10-days bed rest and moderate training on LBNP tolerance in young woman.

The tolerable capacity against LBNP was decreased by bed rest and recovered by physical training. The tolerable capacity was related to VO2max and LVEDd. However, the LBNP tolerance capacity should be primarily limited by factors involving venous return in LVEDd, because VO2max must be controlled by the factors.