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Degraded melanocores are incompetent to protect epidermal keratinocytes against UV damage
Open accessAbstract
Melanosomes are membrane-bound intracellular organelles that are uniquely generated by melanocytes (MCs) in the basal layer of human epidermis. Highly pigmented mature melanosomes are transferred from MCs to keratinocytes (KCs), and then positioned in the supra-nuclear region to ensure protection against ultraviolet radiation (UVR). However, the molecular mechanism underlying melanosome (or melanin pigment) transfer remains enigmatic. Emerging evidence shows that exo-/endo-cytosis of the melanosome core (termed melanocore) has been considered as the main transfer manner between MCs and KCs. As KCs in the skin migrate up from the basal layer and undergo terminal differentiation, the melanocores they have taken up from MCs are subjected to degradation. In this study, we isolated individual melanocores from human MCs in culture and then induced their destruction/disruption using a physical approach. The results demonstrate that the ultrastructural integrity of melanocores is essential for their antioxidant and photoprotective properties. In addition, we also show that cathepsin V (CTSV), a lysosomal acid protease, is involved in melanocore degradation in calcium-induced differentiated KCs and is also suppressed in KCs following exposure to UVA or UVB radiation. Thus, our study demonstrates that change in the proportion of melanocores in the intact/undegraded state by CTSV-related degradation in KCs affects photoprotection of the skin.
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In keratinocytes, autophagic/lysosomal activities inversely correlate with skin color, being higher in keratinocytes derived from light skins than in those from dark skins, independently of keratinocyte differentiation status.
“In keratinocytes, the autophagic/lysosomal activities were described to inversely correlate with skin color, i.e., higher in keratinocytes derived from light skins than in those from dark skins, independently of the keratinocyte differentiation status [ 93 , 96 , 97 , 98 , 99 , 100 ]”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [97]
The Results section ('Up-regulation of CTSV in calcium-induced KCs differentiation increases melanocore degradation'; page unavailable) shows that a lysosomal protease and melanocore degradation increase with keratinocyte differentiation. The References list studies relating hydrolytic enzymes or cathepsin L2 to skin color, but this paper does not establish higher overall autophagic/lysosomal activity in light-skin-derived keratinocytes or show that such a difference is independent of differentiation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIncreased autophagic/lysosomal activities in light skins compared with dark ones suggest the existence of distinct melanin degradation capacities by keratinocytes from different phototypes.
“In particular, the increased autophagic/lysosomal activities in light skins, when compared with dark ones, suggest the existence of distinct melanin degradation capacities by keratinocytes from different phototypes [ 93 , 96 , 97 , 98 , 99 , 100 ]”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [97]
The discussion (page unavailable) links melanocore degradation in keratinocytes to a lysosomal protease and proposes an autophagic/lysosomal pathway. The References list studies of differing enzyme expression and melanosome degradation in light versus dark skin, but this paper does not itself state that autophagic/lysosomal activity is higher in light skin. (LLM, conf=0.82)
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Metadata
- Authors
- Yi, W.-J., Su, M.-Y., Shi, Y., Jiang, S., Xu, S.-Z., & Lei, T.-C.
- Affiliations
- Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Renmin Hospital of Wuhan University (CN)
- ORCID
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2018-04-03
- Volume
- 17
- Issue
- 7
- Pages
- 844-857
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC6056223
- OpenAlex
- W2796456954
- Cited by
- 13
- References
- 33
- Citations by year
- 2025: 4 · 2023: 4 · 2021: 3 · 2019: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81371717, 81573028)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- melanosome transfer, keratinocytes, melanocytes, UV damage, photoprotection, cathepsin V, melanosome degradation, melanin, calcium-induced differentiation, UVA, UV-B radiation, antioxidant activity, lysosomal proteolysis
- MeSH terms
- Antioxidants, Biological Transport, Cathepsins, Cell Differentiation, Cell Fractionation, Cysteine Endopeptidases, Fibroblasts, Humans, Male, Melanins, Melanocytes, Ultraviolet Rays, Keratinocytes, Gene Expression, Melanosomes, Foreskin, Proteolysis, Primary Cell Culture
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