Document Detail

Feedback Control of Adrenal Steroidogenesis via H(2)O(2)-Dependent, Reversible Inactivation of Peroxiredoxin III in Mitochondria.
MedLine Citation:
PMID:  22681886     Owner:  NLM     Status:  In-Data-Review    
Certain members of the peroxiredoxin (Prx) family undergo inactivation through hyperoxidation of the catalytic cysteine to sulfinic acid during catalysis and are reactivated by sulfiredoxin; however, the physiological significance of this reversible regulatory process is unclear. We now show that PrxIII in mouse adrenal cortex is inactivated by H(2)O(2) produced by cytochrome P450 enzymes during corticosterone production stimulated by adrenocorticotropic hormone. Inactivation of PrxIII triggers a sequence of events including accumulation of H(2)O(2), activation of p38 mitogen-activated protein kinase, suppression of steroidogenic acute regulatory protein synthesis, and inhibition of steroidogenesis. Interestingly, levels of inactivated PrxIII, activated p38, and sulfiredoxin display circadian oscillations. Steroidogenic tissue-specific ablation of sulfiredoxin in mice resulted in the persistent accumulation of inactive PrxIII and suppression of the adrenal circadian rhythm of corticosterone production. The coupling of CYP11B1 activity to PrxIII inactivation provides a feedback regulatory mechanism for steroidogenesis that functions independently of the hypothalamic-pituitary-adrenal axis.
In Sup Kil; Se Kyoung Lee; Keun Woo Ryu; Hyun Ae Woo; Meng-Chun Hu; Soo Han Bae; Sue Goo Rhee
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular cell     Volume:  46     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  584-94     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
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