Decreased methionine sulphoxide reductase A expression renders melanocytes more sensitive to oxidative stress: a possible cause for melanocyte loss in vitiligo

Abstract

Background: Methionine is one of the major targets of reactive oxygen species (ROS). It is readily oxidized to methionine-S-sulphoxide and methionine-R-sulphoxide, which can be reduced by methionine sulphoxide reductase (MSR) A and B, respectively. MSR represents a unique repair mechanism in the skin antioxidant network. It functions both as a protein repairer and as a ROS scavenger. However, the expression and activity of MSR are significantly reduced in vitiligo.

Objectives: To investigate whether the decreased expression of MSRA is one of the reasons why melanocytes are especially vulnerable to oxidative stress in vitiligo. Methods We downregulated MSRA expression in immortalized human epidermal melanocyte cell line PIG1 by using the short interfering RNA (siRNA)-targeted gene silencing method. We checked the changes in MSRA transcript and protein level by using reverse transcriptase-polymerase chain reaction and Western blot, respectively. Then we monitored the viability of MSRA-silenced melanocytes under oxidative stress. All statistical analysis was performed by unpaired two-tailed Student's t-test.

Results: The siRNA specific for MSRA successfully suppressed MSRA expression in melanocytes. The lower MSRA expression in melanocytes led to an increased sensitivity to oxidative stress, resulting in more cell death. Furthermore, a remarkable loss of viable cells was found in MSRA-silenced melanocytes even in the absence of exogenously added oxidative stress.

Conclusions: MSRA is crucial for melanocytes to fight against oxidative stress in vitiligo. In addition, it is also important for normal cell survival. Any means to enhance MSRA appears to have therapeutic potential for the treatment of vitiligo.