Functioning methionine sulfoxide reductases A and B are present in human epidermal melanocytes in the cytosol and in the nucleus.
Oxidation of methionine residues by reactive oxygen (ROS) in protein structures leads to the formation of methionine sulfoxide which can consequently lead to a plethora of impaired functionality. The generation of methionine sulfoxide yields ultimately a diastereomeric mixture of the S and R sulfoxides. So far two distinct enzyme families have been identified. MSRA reduces methionine S-sulfoxide, while MSRB reduces the R-diastereomer. It has been shown that these enzymes are involved in regulation of protein function and in elimination of ROS via reversible methionine formation besides protein repair. Importantly, both enzymes require coupling to the NADPH/thioredoxin reductase/thioredoxin electron donor system. In this report, we show for the first time the expression and function of both sulfoxide reductases together with thioredoxin reductase in the cytosol as well as in the nucleus of epidermal melanocytes which are especially sensitive to ROS. Since this cell resides in the basal layer of the epidermis and its numbers and functions are reduced upon ageing and for instance also in depigmentation processes, we believe that this discovery adds an intricate repair mechanism to melanocyte homeostasis and survival.
Clinical and Experimental Dermatology/Department of Biomedical Sciences, University of Bradford, UK. K.Schallreuter@bradford.ac.uk
Karin U
KU
Schallreuter
Katharina
K
Rübsam
Bhaven
B
Chavan
Carsten
C
Zothner
Johanna M
JM
Gillbro
Jennifer D
JD
Spencer
John M
JM
Wood
D002458:Cell Fractionation; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology*; D004579:Electron Transport; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000201:enzymology*; D051150:Methionine Sulfoxide Reductases; D008840:Microfilament Proteins; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014157:Transcription Factors
D007527:Isoenzymes; D008840:Microfilament Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D010088:Oxidoreductases; D013880:Thioredoxin-Disulfide Reductase; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase