title: Attenuated store-operated divalent cation entry and association between STIM1, Orai1, hTRPC1 and hTRPC6 in platelets from type 2 diabetic patients.
abstract: 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.
authors.affiliation: Department of Physiology, Cell Physiology Research Group, University of Extremadura, Cáceres. Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardín
authors.forename: Jose J
authors.initials: JJ
authors.lastname: López
authors.forename: Hanene
authors.initials: H
authors.lastname: Zbidi
authors.forename: Aghleb
authors.initials: A
authors.lastname: Bartegi
authors.forename: Ginés M
authors.initials: GM
authors.lastname: Salido
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D011485:Protein Binding / Q000187:drug effects; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050051:Transient Receptor Potential Channels; D019284:Thapsigargin; D013917:Thrombin; D002118:Calcium