Oxidative stress-induced calreticulin expression and translocation: new insights into the destruction of melanocytes.

Oxidative stress-induced calreticulin expression and translocation: new insights into the destruction of melanocytes.
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氧化应激诱导的钙网蛋白表达和易位:对黑色素细胞破坏的新见解。

DOI:
10.1038/jid.2013.268
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发表时间:
2014
影响因子:
6.5
通讯作者:
刘玲
刘玲
中科院分区:
医学1区
文献类型:
--
作者:
刘玲

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增加的活性氧(ROS)通过自身免疫促进黑素细胞凋亡和皮肤疾病或病症的发展。然而,ROS和自身免疫之间的机制和相互关系是未知的。本研究旨在探讨钙网蛋白(CRT)在过氧化氢(H2 O2)诱导黑素细胞凋亡中的作用。总CRT水平增加的时间依赖性的方式在人类永生化的正常和白癜风黑素细胞暴露于H2 O2诱导的氧化应激,CRT的表面水平增加。此外,CRT过表达增加过氧化氢诱导的细胞凋亡,而敲低显示相反的结果。此外,CRT处理的外周血单核细胞(PBMC)或应激黑素细胞表达的IL-6和肿瘤坏死因子-α(TNF-α)水平高于未处理细胞(P 0.05); CRT敲除可抑制该效应。在体内模型中,CRT水平与白癜风患者的病变面积(R=0.7582,P 0.0001)和持续时间(P0.001)呈正相关。ELISA分析显示,白癜风患者CRT表达高于健康人(P0.05)。这些数据表明,CRT曝光通过H2 O2诱导的氧化应激在黑素细胞凋亡中起着重要的作用,并建议黑素细胞破坏过程中的细胞凋亡和免疫反应之间的关系。
Increased reactive oxygen species (ROS) contribute to melanocyte apoptosis and the development of cutaneous diseases or disorders via autoimmunity. However, the mechanisms and interrelationships between ROS and autoimmunity are unknown. This study aimed to investigate the role of calreticulin (CRT) in hydrogen peroxide (H2O2)-induced apoptosis in melanocytes. Total CRT levels increased in a time-dependent manner in human immortalized normal and vitiligo melanocytes exposed to H2O2-induced oxidative stress, and surface levels of CRT were increased. Moreover, CRT overexpression increased H2O2-induced apoptosis, whereas knockdown showed the opposite results. Furthermore, CRT-treated peripheral blood mononuclear cells (PBMCs) or stressed melanocytes expressed higher levels of IL-6 and tumor necrosis factor-α (TNF-α) than untreated cells (P<0.05); this effect was inhibited with CRT knockdown. In an in vivo model, CRT levels were positively correlated with lesion area (R=0.7582, P<0.0001) and duration of vitiligo in patients (P<0.001). ELISA analyses revealed that CRT expression was higher in vitiligo patients as compared with healthy subjects (P<0.05). These data demonstrate that CRT exposure via H2O2-induced oxidative stress plays a significant role in melanocyte apoptosis and suggest a relationship between apoptosis and immune reactions during melanocyte destruction.
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