Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation-The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation.

Abstract

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

• Authors: Jakub Rok, Zuzanna Rzepka, Justyna Kowalska, Klaudia Banach, Artur Beberok, Dorota Wrześniok
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 7 (Apr 04 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33916535 (Publication Type: Journal Article)

Chemical References

• MITF protein, human
• Microphthalmia-Associated Transcription Factor
• PMEL protein, human
• gp100 Melanoma Antigen
• Monophenol Monooxygenase
• Minocycline

Topics

• Humans
• Melanocytes (cytology, metabolism)
• Microphthalmia-Associated Transcription Factor (biosynthesis)
• Minocycline (pharmacology)
• Monophenol Monooxygenase (biosynthesis)
• Skin Pigmentation (drug effects, radiation effects)
• Ultraviolet Rays
• gp100 Melanoma Antigen (biosynthesis)