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

Author:

Li Fan1ORCID,Liu Hongli12ORCID,Wu Xiaojing1,Song Zhicheng1,Tang Haojia1,Gong Maohua1,Liu Lei1ORCID,Li Fuchang1ORCID

Affiliation:

1. Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian 271018, China

2. Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Department of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China

Abstract

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.

Funder

Natural Science Foundation of China

CARS

Natural Science Foundation of Shandong Province

Special Economic Animal Industry Technology System of Shandong Province

Agricultural Seed Improvement Project of Shandong Province

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference51 articles.

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