Document Detail


FKBP52 is involved in the regulation of SOCE channels in the human platelets and MEG 01 cells.
MedLine Citation:
PMID:  23228564     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Immunophilins are FK506-binding proteins that have been involved in the regulation of calcium homeostasis, either by modulating Ca(2+) channels located in the plasma membrane or in the rough endoplasmic reticulum (RE). We have investigated whether Immunophilins would participate in the regulation of SOCE in human platelets and MEG 01. Both cell types were loaded with fura-2 for determining cytosolic calcium concentration changes ([Ca(2+)](c)), or stimulated and fixed to evaluate the proteins interaction profile by performing immunoprecipitation and Western blotting. We have found that incubation of platelets with FK506 increases Ca(2+) mobilization. TG-evoked, Thr-evoked SOCE and TG-evoked Mn(2+) entry resulted significantly reduced by treatment of platelets with Immunophilins antagonists. We confirmed by immunoprecipitation that Immunophilins interact with TRPC1 and Orai1 in human platelets. FK506 and rapamycin reduced the association between TRPC1 and Orai 1 with FKBP52 in human platelets, and between TRPC1 and the type II IP(3)R, which association is known to be crucial for the maintenance of SOCE in human platelets. FKBP52 role in SOCE activation was confirmed by silencing FKBP52 using SiRNA FKBP52 in MEG 01 as demonstrated by single cell configuration imaging technique. TRPC1 silencing and depletion of cell of TRPC1 and FKBP52 simultaneously, impair activation of SOCE evoked by TG in MEG 01. Finally, in MEG 01 incubated with FK506 we observed a reduction in TRPC1/FKBP52 coupling, and similarly, FKBP52 silencing reduced association between IP3R type II and TRPC1 during SOCE. All together, these results demonstrate that Immunophilins participate in the regulation of SOCE in human platelets.
Authors:
Esther López; Alejandro Berna-Erro; Ginés M Salido; Juan A Rosado; Pedro C Redondo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-7
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
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