Tetrathiomolybdate Decreases the Expression of Alkaline Phosphatase in Dermal Papilla Cells by Increasing Mitochondrial ROS Production.

Dermal papilla cells (DPCs) play important roles in hair growth regulation. However, strategies to regrow hair are lacking. Here, global proteomic profiling identified the tetrathiomolybdate (TM)-mediated inactivation of copper (Cu) depletion-dependent mitochondrial cytochrome c oxidase (COX) as the primary metabolic defect in DPCs, leading to decreased Adenosine Triphosphate (ATP) production, mitochondrial membrane potential depolarization, increased total cellular reactive oxygen species (ROS) levels, and reduced expression of the key marker of hair growth in DPCs. By using several known mitochondrial inhibitors, we found that excessive ROS production was responsible for the impairment of DPC function. We therefore subsequently showed that two ROS scavengers, N-acetyl cysteine (NAC) and ascorbic acid (AA), partially prevented the TM- and ROS-mediated inhibition of alkaline phosphatase (ALP). Overall, these findings established a direct link between Cu and the key marker of DPCs, whereby copper depletion strongly impaired the key marker of hair growth in the DPCs by increasing excessive ROS production.

Dietary lysine supplementation improves growth performance and skeletal muscle development in rabbits fed a low protein diet.

The purpose of this study was to investigate the effects on growth of Lysine (Lys) supplementation in a low protein diet. We also investigated the gene or protein expression related to skeletal muscle development and intestinal amino acid transporters, and determined the major signalling associated with Lys-regulating skeletal muscle development. 1000 healthy, weights averaging 938.6 ± 6.54 g weaned rabbits were randomly divided into five groups (five replicates in each group and 40 rabbits in each replicate). These groups consisted of the normal protein group (NP group, consuming a diet containing 16.27% protein), the low protein group (LP group, 14.15%-14.19% protein) and the LP group with an addition of 0.15%, 0.3% or 0.45% Lys. The trial included 7 d of pre-feeding and 28 d of exposure to the treatment. Compared with NP diet and LP diet, LP+0.3% Lys group improved growth performance (p < 0.05), full-bore weight and half-bore weight of rabbits (p < 0.05). The LP+0.3% Lys group also resulted in a decrease in the excretion of faecal nitrogen and urinary nitrogen (FN; UN; p < 0.05), and an increase in nitrogen utilisation rate (NUR; p < 0.05). LP diet increased the mRNA expression of MSTN and WWP1, and decreased the mRNA expression of IGF1 (p < 0.05). LP diet decreased the protein expression of P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group attenuated the effects of LP diet on the expression of MSTN, WWP1, IGF1, P-P70S6K1, P-4EBP1 and P-S6 (p < 0.05). LP+0.3% Lys group resulted in an increase in mRNA expression of MyoD and protein expression of P-mTOR relative to the NP and LP groups (p < 0.05). In summary, the addition of Lys to a LP diet provides a theoretical basis for the popularisation and application of Lys in rabbit production.