Silencing of PMEL attenuates melanization via activating lysosomes and degradation of tyrosinase by lysosomes
- Central Laboratory of Shaanxi Provincial People's Hospital, Xi'an, Shaanxi (China)
- Department of Clinical Laboratory, Northwest Women and Children's Hospital, Xi'an, Shaanxi (China)
- Department of Dermatology, The General Hospital of the Air Force, Beijing (China)
- Institute of Basic and Translational Medicine, Xi'an Medical University, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an, Shaanxi (China)
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, Shaanxi (China)
Highlights: • Melanin content in human melanocytes was greatly reduced by silencing of PMEL. • Silencing of PMEL reduced the protein level of tyrosinase but did not affect tyrosinase gene expression. • Lysosomes were activated in the absence of PMEL. • PMEL silencing causes tyrosinase degradation by lysosome proteases. The functionally specialized melanosome is a membrane-enclosed lysosome-related organelle, which coexists with lysosomes in melanocytes. Pre-melanosomal protein (PMEL) initiates pre-melanosome morphogenesis and is the only cell-specific pigment protein required for the formation of fibrils on which melanin is deposited in melanosomes. But the effects of PMEL on melanin synthesis and lysosome activity remain unclear. In the study, PMEL was silenced in human epidermal melanocytes by siRNA transfection. Compared to the non-treated group, melanin content in the transfected cells was greatly reduced. Real-time qPCR, Western blotting and immunofluorescence analyses all showed that PMEL-siRNA transfection reduced protein level of tyrosinase, a key enzyme in melanogenesis, but it does not affect tyrosinase gene expression. Moreover, in the absence of PMEL, lysosomal activation was manifested by an increase in the number of lysosomes and activity of hydrolysis enzymes. The lysosome inhibitors restored tyrosinase expression after PMEL silencing, indicating that tyrosinase was degradated by lysosomes. The data collectively showed that silencing of PMEL suppressed melanization through activating lysosomes and degradation of tyrosinase by lysosomes. Our findings provide novel insight into the interaction between the melanosome and its related organelle, the lysosome, supplying a new idea for the pathogenesis and clinical treatment of pigmented diseases.
- OSTI ID:
- 23103627
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 4; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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