Abstract
Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. We demonstrated that ATG7-dependent autophagy could affect melanin content of melanocytes by regulating melanogenesis. Moreover, suppression of ATG7-dependent autophagy inhibits proliferation and promotes oxidative stress-induced apoptosis of melanocytes, whereas enhancement of ATG7-dependent autophagy protects melanocytes from oxidative stress-induced apoptosis. Meanwhile, deficiency of ATG7-dependent autophagy results in premature senescence of melanocytes under oxidative stress. Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.
Highlights
Human skin is directly and constantly under the risks of numerous oxidative environmental stressors, such as ultraviolet (UV) irradiation, air pollutants, and chemical products
Quantitative reverse transcriptase in real-time PCR analysis showed that the mRNA expression of ATG7 in natural human epidermal melanocytes (NHEMs) was significantly decreased in ATG7 short hairpin RNA (shRNA) group (Fig.1a)
Western blotting analysis further demonstrated that the protein expression of ATG7 in melanocytes was diminished in ATG7 shRNA group
Summary
Human skin is directly and constantly under the risks of numerous oxidative environmental stressors, such as ultraviolet (UV) irradiation, air pollutants, and chemical products. Redox balance between free radicals and antioxidants, which detoxify their harmful effects is critical for maintaining normal functions of various skin cell types, including keratinocytes, melanocytes, and fibroblast[1,2,3]. Excessive oxidative stress may lead to skin problems, especially aging[4] and skin cancer[5]. Reactive oxygen species (ROS) can attack melanocytes and interfere with normal metabolism, proliferation, and differentiation of melanocytes, which ends up causing cell apoptosis and defects[11]. Studies have indicated that dysfunction of the anti-oxidative system in patients with vitiligo may increase the vulnerability of melanocytes to oxidative damage. Accumulation of ROS will further lead to the impairment of redox homeostasis and result in the destruction of melanocytes[12,13]. Effective treatment options for vitiligo are still lacking[14], driving researchers to seek potential new therapies
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