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Role of the aryl hydrocarbon receptor signaling pathway in promoting mitochondrial biogenesis against oxidative damage in human melanocytes.

Abstract：

BACKGROUND:Reactive oxygen species (ROS)-induced mitochondrial damage aggravates oxidative stress and activates mitochondrial apoptosis pathway to mediate melanocyte death. However, the repair mechanisms underlying damaged mitochondria of melanocytes remain unclear. Accumulative evidence has revealed that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a vital role in maintaining mitochondrial homeostasis. OBJECTIVE:To investigate whether the AHR signaling pathway could protect human melanocytes from oxidative damage through controlling mitochondrial quality. METHODS:We constructed an oxidative stress model of melanocytes with hydrogen peroxide (H2O2) in the human normal melanocyte PIG1 cell line, and detected ROS level, apoptosis, mitochondrial ROS level, mitochondrial membrane potential, ATP production, mitochondrial DNA and mitochondrial modulators after co-treatment with AHR ligand or antagonist and H2O2 in the PIG1 cells. RESULTS:In the present study, we found that H2O2-induced oxidative stress directly activated the AHR signaling pathway in melanocytes, whereas abnormal activation of AHR signaling pathway enhanced oxidative damage to mitochondria and melanocytes. Further studies showed that the AHR signaling pathway promoted mitochondrial DNA synthesis and ATP production probably by regulating the expression of nuclear respiratory factor 1 (NRF1) and its downstream targets. CONCLUSION:Our findings reveal that the AHR signaling pathway might have a major role in protecting melanocytes against oxidative damage via inducing mitochondrial biogenesis, while impaired AHR activation could cause defective repair of mitochondria and exacerbate oxidative damage-induced apoptosis in melanocytes. Our data suggest that the AHR signaling pathway might be a novel mechanism of mitochondrial biogenesis involved in protecting melanocytes from oxidative stress.

journal_name

J Dermatol Sci

journal_title

Journal of dermatological science

authors

Wang X,Li S,Liu L,Jian Z,Cui T,Yang Y,Guo S,Yi X,Wang G,Li C,Gao T,Li K

doi

10.1016/j.jdermsci.2019.09.001

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

33-41

issue

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(19)30290-7

journal_volume

pub_type

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Role of the aryl hydrocarbon receptor signaling pathway in promoting mitochondrial biogenesis against oxidative damage in human melanocytes.