Copper (Cu) is known to induce oxidative stress and apoptosis in the liver, kidney, and brain. We previously demonstrated the molecular mechanism underlying the Cu-induced hepatic diurnal variation. However, the cellular molecule(s) involved in Cu-induced renal chronotoxicity remain unknown. In this study, we aimed to elucidate the molecular mechanisms underlying Cu-induced diurnal toxicity in the kidneys. We evaluated cell viability and clock gene expression levels in mouse renal cortex tubular cells (MuRTE61 cells) after Cu treatment. We also examined the Cu homeostasis- and apoptosis-related gene levels after period 1 (Per1) overexpression in MuRTE61 cells. Cu treatment decreased MuRTE61 cell viability in a dose-dependent manner. It increased the Per1 expression levels after 24 h. Notably, Per1 overexpression alleviated the Cu-induced inhibition of MuRTE61 cell viability. Moreover, Per1 overexpression downregulated the cleaved caspase-3 and reduced Cu levels by upregulating the antioxidant 1 copper chaperone (Atox1) levels. These results suggest that Cu-induced renal toxicity is associated with Per1 expression via the regulation of the copper chaperone, Atox1.

Linalool and linalyl acetate are major components of lavender essential oil. These substances possess many biological activities, such as anti-inflammatory activity, analgesic and anxiolytic effects, and anticonvulsant properties, and they also induce modulation of neuronal activity in the autonomic nervous system. However, there are no reports of the direct effects of linalool on respiratory activity. In the present study, we analyzed the effects of linalool and linalyl acetate on central respiratory activity in the brainstem-spinal cord preparation isolated from newborn rats. Linalool dose-dependently decreased the rate of respiratory activity. This effect was reversed by bicuculline, suggesting that linalool enhanced inhibitory synaptic connections via GABAA receptors. In addition, linalool reduced the coefficient of variation of inspiratory burst intervals and thus could work to stabilize the respiratory rhythm. Linalyl acetate did not cause inhibitory effects as observed in linalool treatment. Linalool depressed burst activity of pre-inspiratory neurons in the medullary respiratory networks and increased the amplitude of inspiratory inhibitory postsynaptic potentials of pre-inspiratory neurons. We concluded that linalool caused inhibitory effects on respiratory rhythm generation mainly through activation of presynaptic GABAA receptors of pre-inspiratory neurons.

Exercise training increases brain-derived neurotrophic factor (BDNF) expression and improves cognitive function. However, the dynamics of BDNF during inactivity and the effects of exercise intervention on BDNF levels have rarely been examined. Therefore, we aimed to examine changes in serum, skeletal muscle, and brain BDNF levels under these conditions. Mice were divided into control (Co), cast immobilization (CI), reloading (RL), and exercise (Ex) groups. Muscle atrophy was induced by cast immobilization for 2 weeks in the CI, RL, and Ex groups. After cast removal, the RL and Ex groups underwent regrounding and treadmill exercise, respectively, for 2 weeks. Serum, skeletal muscle, and brain BDNF levels showed a similar decreasing trend in the CI group, recovery in the RL group, and a further increase in the Ex group compared with those in the Co group. This indicates that BDNF levels change in parallel with the degree of activity. However, the magnitude of variation differed among the tissues in the order of serum > skeletal muscle > brain tissue. These results suggest that different mechanisms in different tissues regulate BDNF expression. BDNF could potentially act as an objective measure of the impact of both inactivity and exercise-based interventions.

Sarcopenia is a common complication of chronic kidney disease (CKD) and has a detrimental effect on prognosis. Previous studies have explored the role of secondary calciprotein particles (CPP2) in determining the progression of complications and poor outcomes in patients with CKD. However, no study has demonstrated that CPP2 impairs skeletal myogenesis. Our study revealed that CPP2 exposure inhibits skeletal myogenesis by suppressing myotube formation and expression of skeletal muscle-specific myosin heavy chain and actin in human primary myoblasts. Moreover, CPP2 exposure altered the expression patterns of lineage-determinative transcription factors responsible for regulating myotube differentiation marker genes. This study first demonstrated that CPP2 interferes with myoblast differentiation and myotube formation in vitro.