Research Papers:
MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling
Metrics: PDF 2694 views | HTML 3843 views | ?
Abstract
Bo Yang1, Qiu-Yun Xu2, Chun-Yan Guo2, Jin-Wen Huang2, Shu-Mei Wang2, Yong-Mei Li1, Ying Tu3, Li He3, Zhi-Gang Bi4, Chao Ji2, Bo Cheng2
1Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
2Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
3Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming, China
4Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing, China
Correspondence to:
Bo Cheng, email: [email protected]
Chao Ji, email: [email protected]
Keywords: ultra violet (UV), skin cell damage, MHY1485, mTOR, Nrf2
Received: October 19, 2016 Accepted: December 08, 2016 Published: January 04, 2017
ABSTRACT
Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling.
![Creative Commons License](/images/80x15.png)
PII: 14299