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In these cases, H2O2 would induce the demethylation of the promoter region of the TRPM2 gene and increase its expression in melanocytes, promoting the calcium influx into the cytoplasm, and promoting its apoptosis.59 In a study with murine melanocytes, the natural process of autophagy, in which cells degrade their organelles and damaged proteins to maintain their homeostasis, was also shown to be impaired when excessive ROS accumulation occurs.60 In vitiligo, melanocytes and fibroblasts are more sensitive to OS-induced autophagy, which reduces their potential to control melanogenesis.61 OS can also trigger changes in the melanocyte endoplasmic reticulum, culminating in the accumulation of defective proteins, stimulating a cell stress phenomenon called βunfolded protein responseβ (UPR).62 Moreover, energy requirements for protein production (such as melanin) alone generate ROS through mitochondrial metabolism
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[DOI] [PubMed] [Google Scholar] 57.van βt Erve T.J., Wagner B.A., Ryckman K.K., Raife T.J., Buettner G.R
