Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

Abstract

Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesisstimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3', 5'-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and-2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.

The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation

“…The coculture system of B16F10 and HaCaT cells were established on confocal dish, as described previously ( Lee et al, 2015 ; Lv et al, 2020c ). After J147 treatment, the cells were immunostained with anti-GP100 and anti-Cytokeratin according to the standard protocol.…”

Silencing of Rab23 by siRNA inhibits ultraviolet B‐induced melanogenesis via downregulation of PKA / CREB / MITF

“…Ultraviolet B (UVB) is the strongest exogenous factor that enhances melanin synthesis, 2 and UV‐induced melanogenesis plays a vital role in photoprotection 3 . UV irradiation induces the secretion of α‐melanocyte‐stimulating hormone from keratinocytes; this hormone binds to the melanocortin‐1 receptor in melanocytes to increase intracellular cyclic adenosine monophosphate (cAMP) level, subsequently activating the protein kinase A (PKA)/cAMP‐responsive element‐binding (CREB) pathway to promote melanogenesis 4,5 . Biopsy data have revealed that the expression of melanocyte‐specific markers such as microphthalmia transcription factor (MITF), MART1, Pmel17, tyrosinase and dopachrome tautomerase increases after 1 week of UV exposure 6 .…”

“…Melanosomes localize around the cell nucleus through the activity of the endosomal transport system 9 . Developed melanosomes relocate from the perinuclear range to the cell layer by moving along two cytoskeletal components (i.e., microtubules and actin filaments) and are eventually transferred to neighbouring keratinocytes 4 . During this process, Rab27a, myosin Va and melanophilin (Mlph) form a tripartite protein complex involved in the transportation of melanosomes from microtubules to actin fibres 10,11 .…”

Effects of Germination Black Soy Milk Fermented with Lactobacillus plantarum TWK10 on Anti-Oxidative and Anti-Melanogenesis

“…Recently, because melanin is present on the surface of zebrafish embryos and the process of pigmentation can be easily observed without complicated experimental steps, numerous studies have used zebrafish embryos for melanin-related experiments [9]. Detection of important indicators that affect melanogenesis, such as tyrosinase activity, in the zebrafish embryo model is also feasible [10]. In addition, the appearance of zebrafish embryos and heart rate can also be used to evaluate the toxicity of samples [9].…”