Degraded melanocores are incompetent to protect epidermal keratinocytes against UV damage

Abstract

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.

Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?

“…14 Moreover, autophagy can be enhanced by UV radiation 15,16 and two recent studies found that UV exposure increases the expression levels of the lysosomal protease Cathepsin V, leading to increased melanin degradation in keratinocytes. 17,18 Together, these findings suggest that damage caused by UV radiation accumulates with time, triggering melanin degradation.…”

“…Indeed, autophagy has been proposed to regulate melanin content within keratinocytes, as melanin levels in human skin samples are reduced by inducers of autophagy and enhanced by its inhibitors . Moreover, autophagy can be enhanced by UV radiation and two recent studies found that UV exposure increases the expression levels of the lysosomal protease Cathepsin V, leading to increased melanin degradation in keratinocytes . Together, these findings suggest that damage caused by UV radiation accumulates with time, triggering melanin degradation.…”

Tranexamic acid may promote melanocores clustering in keratinocytes through upregulation of Rab5b

“…23 Pmel17/gp100 is well-established as an amyloid fibril component within melanocores, while tyrosinase is the membrane marker for melanosomes. 10 Our results showed that both melanocoreincorporated keratinocytes and MNT-1 cells expressed Pmel17/gp100, while only MNT-1 significantly expressed tyrosinase. Further demonstrating that isolated and transported to NHEK cells in our study were membrane-free melanocores rather than melanosomes.…”

“…As previously described, the melanocores were isolated from MNT-1 cells. 10 Approximately 2 × 10 6 MNT-1 cells were harvested per Eppendorf tube (1.5 mL) and frozen at −20°C. After thawing, 1 mL cold lysis solution was added per Eppendorf tube, kept at 4°C for 20 min, and mixed every 10 min.…”

“…studies suggest that abnormal melanin degradation participates in the pathogenesis of melasma and that autophagy may play a role in melanin degradation. 10,11 Melasma is often refractory to treatment leading to frequent recurrences. Recently, tranexamic acid (TXA) has been reported to have huge prospects for clinical application to treat melasma.…”