Tyrosinase‐catalyzed metabolism of rhododendrol (RD) in B16 melanoma cells: production of RD‐pheomelanin and covalent binding with thiol proteins

@article{Ito2015TyrosinasecatalyzedMO,
  title={Tyrosinase‐catalyzed metabolism of rhododendrol (RD) in B16 melanoma cells: production of RD‐pheomelanin and covalent binding with thiol proteins},
  author={Shosuke Ito and Masae Okura and Yukiko Nakanishi and Makoto Ojika and Kazumasa Wakamatsu and Toshiharu Yamashita},
  journal={Pigment Cell \& Melanoma Research},
  year={2015},
  volume={28}
}
RS‐4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD) was reported to induce leukoderma of the skin. To explore the mechanism underlying that effect, we previously showed that oxidation of RD with mushroom tyrosinase produces RD‐quinone, which is converted to secondary quinone products, and we suggested that those quinones are cytotoxic because they bind to cellular proteins and produce reactive oxygen species. We then confirmed that human tyrosinase can oxidize both enantiomers of RD. In this… 
The potent pro‐oxidant activity of rhododendrol–eumelanin induces cysteine depletion in B16 melanoma cells
TLDR
This study examines the changes in glutathione (GSH) and cysteine in B16 cells exposed to RD for up to 24 h and proposes that RD‐eumelanin induces cytotoxicity through its potent pro‐oxidant activity.
Biochemical Mechanism of Rhododendrol-Induced Leukoderma
TLDR
It is found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products and the results suggest two major mechanisms of cytotoxicity to melanocytes.
NAD(P)H dehydrogenase, quinone 1 (NQO1), protects melanin‐producing cells from cytotoxicity of rhododendrol
TLDR
The results suggest that NQO1 attenuates the cytotoxicity of RD and/or its metabolites and the leukoderma of the skin that may result.
The potent pro‐oxidant activity of rhododendrol–eumelanin is enhanced by ultraviolet A radiation
TLDR
The results suggest that RD–eumelanin is cytotoxic to melanocytes through its potent pro‐oxidant activity that is enhanced by UVA radiation.
4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress
TLDR
UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress and increased generation of intracellular reactive oxygen species (ROS) was detected.
Effects of rhododendrol and its metabolic products on melanocytic cell growth.
Oxidative Oligomerization of DBL Catechol, a Potential Cytotoxic Compound for Melanocytes, Reveals the Occurrence of Novel Ionic Diels-Alder Type Additions
TLDR
The results indicate that DBL quinone formed in the reaction is extremely reactive and undergoes facile dimerization and trimerization reactions to produce multiple isomeric products by novel ionic Diels-Alder type condensation reactions.
The Oxidation of Equol by Tyrosinase Produces a Unique Di-ortho-Quinone: Possible Implications for Melanocyte Toxicity
TLDR
The results suggest that EQ-quinones could be cytotoxic to melanocytes due to their binding to cellular proteins.
Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45.
Biochemical effects of the flavanol‐rich lychee fruit extract on the melanin biosynthesis and reactive oxygen species
TLDR
The results suggest that FRLFE can protect melanocytes from cytotoxicity caused by an excess amount of melanin and ROS in a different manner from resveratrol.
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