Year-end Sale % OFF 
Abstract
Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.
Highlights
Vitiligo is an autoimmune skin disease characterized by chronic depigmentation and milk-white lesions, which result from the destruction of epidermal melanocytes [1]
Previous studies have elucidated various pathways of oxidative stress-induced melanocytes death, like aberrant mitochondrial function, impairment of the antioxidant defense system, and release of cytokines associated with immune reaction activation [3,4,5,6,7], but the modality of melanocytes death was confined to apoptosis and necroptosis
We found that other oxidative stressassociated melanocytes death modalities still existed after the suppression of previously reported apoptosis and necroptosis by
Summary
Vitiligo is an autoimmune skin disease characterized by chronic depigmentation and milk-white lesions, which result from the destruction of epidermal melanocytes [1]. H2O2 induced dephosphorylation of AIFM1 at Ser116, which was a PGAM5 colocalized with mitochondrial marker COX IV in the molecular event specific to oxeiptosis, in melanocytes pretreated control, while KEAP1 lost its colocalization with COX IV in the with Z-VAD-FMK (Z-VAD) and Necrostatin-1 (Nec-1). Presence of H2O2, and pretreatment of PIG1 cells with Z-VAD and KEAP1 and PGAM5, which were in oxeiptosis signaling pathway, Nec-1 did not restore the dissociation of KEAP1 and COX IV were detected to be upregulated in H2O2 treated melanocytes and induced by H2O2 (Fig. 3A, B), which further supported the putative vitiligo lesional skin biopsy. Our study increased in PIG1 cells after the treatment of H2O2, and employing elucidated that oxidative stress could induce melanocytes Z-VAD and Nec-1 in the pretreatment of PIG1 cells did not alter oxeiptosis in vitiligo. The result was further confirmed in the lesional skin of vitiligo patients as detected by immunofluorescence assay when
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
