Testosterone Stimulates Duox1 Activity through GPRC6A in Skin Keratinocytes
- 등재 SCIE, SCOPUS
- 발행기관 AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- 발행년도 2014
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000113023
- 본문언어 영어
- Published As http://dx.doi.org/10.1074/jbc.M114.583450
초록/요약
Testosterone is an endocrine hormone with functions in reproductive organs, anabolic events, and skin homeostasis. We report here that GPRC6A serves as a sensor and mediator of the rapid action of testosterone in epidermal keratinocytes. The silencing of GPRC6A inhibited testosterone-induced intracellular calcium ([Ca2+](i)) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of G(q) protein, IP3 generation, and [Ca2+](i) mobilization, leading to Duox1 activation. H2O2 generation by testosterone stimulated the apoptosis of keratinocytes through the activation of caspase-3. The application of testosterone into three-dimensional skin equivalents increased the apoptosis of keratinocytes between the granular and stratified corneum layers. These results support an understanding of the molecular mechanism of testosterone-dependent apoptosis in which testosterone stimulates H2O2 generation through the activation of Duox1.
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