Homocysteine induces melanocytes apoptosis via PERK–eIF2α–CHOP pathway in vitiligo
Autor: | Qingrong Ni, Chunying Li, Yangzi Tian, Shuli Li, Tongtian Zhuang, Zhe Jian, Kai Li, Pu Song, Tianwen Gao, Tingting Cui, Weigang Zhang, Xiuli Yi, Jiaxi Chen, Ling Liu, Jianru Chen |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male 0301 basic medicine Homocysteine Eukaryotic Initiation Factor-2 Vitiligo Apoptosis CHOP medicine.disease_cause Models Biological eIF-2 Kinase 03 medical and health sciences chemistry.chemical_compound Folic Acid 0302 clinical medicine Depigmentation medicine Humans Protein kinase A Cell Proliferation Melanins chemistry.chemical_classification Reactive oxygen species integumentary system General Medicine Endoplasmic Reticulum Stress medicine.disease 030104 developmental biology chemistry Case-Control Studies Disease Progression Cancer research Melanocytes Female medicine.symptom Transcription Factor CHOP 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
Zdroj: | Clinical Science. 134:1127-1141 |
ISSN: | 1470-8736 0143-5221 |
Popis: | Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)–eukaryotic translation initiation factor 2α (eIF2α)–C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo. |
Databáze: | OpenAIRE |
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