Oxidative Stress–Induced Calreticulin Expression and Translocation: New Insights into the Destruction of Melanocytes

• Published in: Journal of investigative dermatology Vol. 134; no. 1; pp. 183 - 191
• Main Authors: Zhang, Yajun, Liu, Ling, Jin, Liang, Yi, Xiuli, Dang, Erle, Yang, Yang, Li, Chunying, Gao, Tianwen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2014; Elsevier Limited
• Subjects: Antioxidants - metabolism; Apoptosis - drug effects; Apoptosis - physiology; Biological Transport - drug effects; Biological Transport - physiology; Calreticulin - genetics; Calreticulin - metabolism; Cell Line, Transformed; Gene Knockdown Techniques; Humans; Hydrogen Peroxide - pharmacology; Interleukin-6 - metabolism; Melanocytes - cytology; Melanocytes - metabolism; Oxidants - pharmacology; Oxidative Stress - physiology; Tumor Necrosis Factor-alpha - metabolism; Vitiligo - metabolism; Vitiligo - pathology
• DOI: 10.1038/jid.2013.268
• ISSN: 0022-202X; 1523-1747

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.