PMID- 21303733
OWN - NLM
STAT- MEDLINE
DCOM- 20110826
LR  - 20161125
IS  - 1096-0961 (Electronic)
IS  - 1079-9796 (Linking)
VI  - 46
IP  - 3
DP  - 2011 Mar 15
TI  - Attenuated store-operated divalent cation entry and association between STIM1, 
      Orai1, hTRPC1 and hTRPC6 in platelets from type 2 diabetic patients.
PG  - 252-60
LID - 10.1016/j.bcmd.2010.12.008 [doi]
AB  - Agonist-evoked Ca(2+) entry has been reported to be enhanced in platelets from 
      type 2 diabetic patients, which results in altered platelet responsiveness and 
      cardiovascular complications. The present study is aimed to investigate whether 
      store-operated divalent cation entry, a major Ca(2+) entry pathway, is altered in 
      platelets from diabetic patients. Store-operated divalent cation entry was 
      estimated by determination of Mn(2+) entry. Association between STIM1, Orai1, 
      hTRPC1 and hTRPC6 was detected by co-immunoprecipitation and Western blotting. In 
      the presence of specific purinergic and serotoninergic receptor antagonists 
      Mn(2+) entry, induced by thapsigargin (TG), was reduced in platelets from 
      diabetic donors as compared to healthy controls. Treatment with TG or the agonist 
      thrombin enhanced co-immunoprecipitation of STIM1 with Orai1, hTRPC1 and hTRPC6 
      in platelets from healthy donors, a response that was significantly reduced in 
      platelets from diabetic patients. Our results indicate that store-operated 
      divalent cation entry is reduced in platelets from type 2 diabetic subjects, 
      which is likely mediated by impairment of the association of STIM1 with the 
      channel subunits Orai1, hTRPC1 and hTRPC6 and might be involved in the 
      pathogenesis of the altered platelet responsiveness observed in diabetic 
      patients.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Jardin, Isaac
AU  - Jardin I
AD  - Department of Physiology, Cell Physiology Research Group, University of 
      Extremadura, Caceres. Spain.
FAU - Lopez, Jose J
AU  - Lopez JJ
FAU - Zbidi, Hanene
AU  - Zbidi H
FAU - Bartegi, Aghleb
AU  - Bartegi A
FAU - Salido, Gines M
AU  - Salido GM
FAU - Rosado, Juan A
AU  - Rosado JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (Calcium Channels)
RN  - 0 (Cations, Divalent)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (ORAI1 Protein)
RN  - 0 (ORAI1 protein, human)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blood Platelets/drug effects/*metabolism
MH  - Calcium/metabolism
MH  - Calcium Channels/*metabolism
MH  - Cations, Divalent/*metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Middle Aged
MH  - Neoplasm Proteins/*metabolism
MH  - ORAI1 Protein
MH  - Protein Binding/drug effects
MH  - Stromal Interaction Molecule 1
MH  - Thapsigargin/pharmacology
MH  - Thrombin/pharmacology
MH  - Transient Receptor Potential Channels/*metabolism
EDAT- 2011/02/10 06:00
MHDA- 2011/08/30 06:00
CRDT- 2011/02/10 06:00
PHST- 2010/09/23 00:00 [received]
PHST- 2010/11/08 00:00 [revised]
PHST- 2010/12/20 00:00 [accepted]
PHST- 2011/02/10 06:00 [entrez]
PHST- 2011/02/10 06:00 [pubmed]
PHST- 2011/08/30 06:00 [medline]
AID - S1079-9796(10)00338-4 [pii]
AID - 10.1016/j.bcmd.2010.12.008 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 2011 Mar 15;46(3):252-60. doi: 10.1016/j.bcmd.2010.12.008.