Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo

Abstract

Vitiligo is a potentially serious condition characterized by loss of melanin and death of melanocytes. To identify potential therapeutic targets for vitiligo, we conducted a microarray analysis of three human vitiligo specimens and paired adjacent normal tissues. Because we found that the fatty acid desaturase 1 (FADS1) gene was downregulated in vitiligo specimens, we carried out experiments to assess its role in melanocyte replication and survival. RT-qPCR was used to verify that FADS1 expression was lower in vitiligo-affected tissues and vitiligo melanocyte PIG3V cells than in matched controls or normal human epidermal PIG1 melanocytes. In addition, CCK-8, immunofluorescence, western blot and flow cytometry assay were used to detect the proliferation and apoptosis in PIG1 cells respectively. Overexpression of FADS1 promoted proliferation of PIG3V melanocytes, while FADS1 silencing inhibited proliferation and induced cell death in PIG1 melanocytes. Increased ROS generation; induction of mitochondrial-mediated apoptosis via upregulation of Bax and active caspases 3 and 9 and downregulation of Bcl-2; and cell cycle arrest via downregulation of c-Myc and Cyclin D1 and upregulation of p21 were all enhanced after FADS1 silencing in PIG1 melanocytes. These findings implicate FADS1 downregulation in the pathogenesis of vitiligo and may open new avenues for its treatment.

Quantitative mapping of human hair greying and reversal in relation to life stress

“…The upregulation of specific components related to mitochondrial energy metabolism in white hairs suggests that energy metabolism regulates not only hair growth as previously demonstrated ( Flores et al, 2017 ; Mancino et al, 2020 ; Vidali et al, 2014 ) but also HF greying biology. Our findings demonstrating an upregulation of the fatty acid synthesis and metabolism machinery resonate particularly strongly with recent work demonstrating that fatty acid synthesis by FASN ( Fafián-Labora et al, 2019 ) and transport by CPT1a ( Seok et al, 2020 ) are sufficient drivers of cell senescence, and that fatty acid metabolism regulates melanocyte aging biology ( Tang et al, 2019 ). Approaches combining both high molecular and spatial resolution may be particularly informative ( Vyumvuhore et al, 2021 ).…”

Discovering the Protective Effects of Resveratrol on Aflatoxin B1-Induced Toxicity: A Whole Transcriptomic Study in a Bovine Hepatocyte Cell Line

“…FADS1 plays a role in the synthesis of long chain polyunsaturated fatty acids (PUFA) occurring in liver, and controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Notably, in human melanocytes, FADS1 downregulation induced cell cycle arrest and cell death via ROS generation and mitochondria-mediated apoptosis [ 77 ]. Indirectly, this evidence let us think that FADS1 induction in BFH12 treated with R might have beneficial effects.…”

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T)

“…Many of the mechanisms contributing to skin aging are not fully understood; nevertheless, it is clear that mitochondria play an important role within a complex network ( Birket and Birch-Machin, 2007 ; Hudson et al, 2016 ; Gu et al, 2020 ). Among them, mitochondria metabolism of substances like melanin maintain intracellular homeostasis by photoprotective processes ( Naidoo et al, 2018 ; Tang et al, 2019 ). As a result, the accumulation of small abnormalities or deficits may lead to larger negative effects on the skin and its components if cells endogenous mitochondria is not treated.…”

“…This is how mitochondrial damage may contribute to an alteration of skin pigmentation and aging. Melanocyte degeneration, cell cycle arrest, and apoptosis have been associated with oxidative stress due to mitochondrial dysfunction in Vitiligo ( Tang et al, 2019 ; Yi et al, 2019 ).…”