Effect of thioredoxin reductase 1 on glucocorticoid receptor activity in human outer root sheath cells.
Alopecia areata (AA) is a common disease of patchy hair loss on the scalp that can progress to cover the entire scalp and eventually the entire body. Intralesional injection of corticosteroids is the first-line therapy for adult patients, however some patients do not respond to glucocorticoid treatment effectively. To delineate the molecular mechanism underlying glucocorticoid insensitivity, we examined the expression of glucocorticoid receptor (GR) and thioredoxin reductase 1 (TrxR1). In some case of glucocorticoid-resistant AA patients, the expression of TrxR1 was decreased in outer root sheath (ORS). We then investigated the effect of TrxR1 on GR activity using recombinant adenoviruses. Overexpression of TrxR1 markedly increased GR activity in ORS cells cultured in vitro. In addition, TrxR1 protected GR activity against H(2)O(2). Finally, TrxR1-enhanced GR activity was significantly inhibited by the overexpression of dominant negative form of Trx (Trx(C32S/C35S)). These results suggest that decreased TrxR1 may be one putative cause for glucocorticoid resistance in AA, through the impact on intracellular redox system.
Sohn
Kyung-Cheol
KC
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 640 Daesa-dong, Daejeon 301-040, Republic of Korea.
Jang
Sunhyae
S
Choi
Dae-Kyoung
DK
Lee
Young-Sook
YS
Yoon
Tae-Jin
TJ
Jeon
Eun Kyoung
EK
Kim
Kyung Ho
KH
Seo
Young-Joon
YJ
Lee
Jeung-Hoon
JH
Park
Jang-Kyu
JK
Kim
Chang Deok
CD
D000506:Alopecia Areata / Q000503:physiopathology*; D004351:Drug Resistance; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012535:Scalp / Q000166:cytology; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D013879:Thioredoxins; D006861:Hydrogen Peroxide; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase