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H 2 O 2 ‐induced oxidative stress disrupts mitochondrial functions and impairs migratory potential of human epidermal melanocytes
Author(s) -
Xu Ping,
Xue YanNing,
Ji HuiHui,
Tan Cheng,
Guo Shun
Publication year - 2020
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14134
Subject(s) - mitochondrion , oxidative stress , microbiology and biotechnology , reactive oxygen species , cytochrome c oxidase , oxidative phosphorylation , biology , melanocyte , atp synthase , mitochondrial ros , mitochondrial permeability transition pore , adenosine triphosphate , biochemistry , apoptosis , programmed cell death , enzyme , genetics , melanoma
Reactive oxygen species (ROS) have already been demonstrated to impede the migratory ability in non‐melanocytic cell lines by depleting mitochondrial ATP production. Therefore, understanding the mitochondrial metabolic response to migration in the presence of ROS should be a key to understanding repigmentation in vitiligo. This study aimed to investigate the energy mechanism associated with the ROS‐mediated attenuation of melanocyte migration. After melanocytes were pretreated with H 2 O 2 , their ATP production, migratory ability, ultrastructural changes and Mitochondrial Permeability Potential were analysed. The results showed that, in parallel with the decreased ATP production, the migratory ability of melanocytes was significantly inhibited by oxidative stress. Supplementation with exogenous ATP reversed the suppressed ATP‐dependent migration of melanocytes. Melanocytes were then stressed with H 2 O 2 and Agilent Whole Human Genome microarray analysis identified 763 up‐regulated mRNAs and 1117 down‐regulated mRNAs. Among them, 11 of the encoded proteins were involved in mitochondrial ATP production and their expression levels were verified. The decreased expression of NADH dehydrogenase 2(ND 2) , cytochrome c oxidase 1(COX1) and cytochrome c oxidase 3(COX3) was shown to be involved in the depletion of mitochondrial ATP production, which was coupled with the impaired migratory potential. These results indicate that the migration of melanocytes relies heavily on an inexhaustible supply of ATP from mitochondria.