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Tyrosinase may protect human melanocytes from the cytotoxic effects of the superoxide an ion
Author(s) -
Valverde P.,
Manning P.,
Todd C.,
McNeil C.J.,
Thody A. J.
Publication year - 1996
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1996.tb00125.x
Subject(s) - superoxide , cytotoxic t cell , tyrosinase , chemistry , pharmacology , cancer research , biochemistry , medicine , in vitro , enzyme
Reactive oxygen species (ROS) are potentially cytotoxic and several mechanisms have evolved to protect against their damaging effects. In melanocytes, tyrosinase may have such a role by utilising the superoxide anion (O 2 − )in the production of melanin. In the present study, we have examined the cytotoxic effects of O 2 − and hydrogen peroxide (H 2 O 2 ) in human melanocytes both before and following the activation of tyrosinase. Xanthine oxidase (XO, 5–150 mU · ml −1 ) and glucose oxidase (GO, 0.1‐20 mU · ml −1 ) were used to generate the O 2 − and H 2 O 2 respectively, and the cytotoxic effects assessed by measuring cell survival using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2.5 diphenyltetrazolium (MTT) assay. 3 h later, dose related decreases in melanocyte survival were seen. Similar experiments with keratinocytes and libroblasts showed that these cells were more resistant to the cytotoxic effects of O 2 − than were the melanocytes. The effect of increasing tyrosinase activity was examined by growing the melanocytes in the presence of an analogue of melano‐cyte‐stimulating hormone (MSH) Nle 4 DPhe 7 α‐MSH (10 −8 M), for 48 h. This increased tyrosinase activity, melanin content, the ability to trap O 2 − and the resistance of the melanocytes to the cytoloxic effects of this ROS. but failed to alter their susceptibility to the damaging effects of H 2 O. Nle 4 DPhe 7 α‐MSH had no effect on the resistance of keratinocytes and libroblasts to either O 2 − or H 2 0 2 . After 3 h, XO. as opposed to GO. also increased the melanin content of human melanocytes; this effect was not accompanied by an increase in tyrosinase activity. The present results suggest that tyrosinase may utilise O 2 − to produce melanin and that this process may protect melanocytes from the potentially damaging effects of this ROS.