PMID- 16928598 OWN - NLM STAT- MEDLINE DCOM- 20061026 LR - 20191210 IS - 0953-7104 (Print) IS - 0953-7104 (Linking) VI - 17 IP - 5 DP - 2006 Aug TI - Endogenously generated reactive oxygen species reduce PMCA activity in platelets from patients with non-insulin-dependent diabetes mellitus. PG - 283-8 AB - Intracellular Ca2+ homeostasis in platelets of patients with non-insulin-dependent diabetes mellitus (NIDDM) has been reported to be altered, leading to an increased adhesiveness and spontaneous aggregation. Among the disturbed Ca2+ mechanism in platelets from NIDDM subjects, a reduced Ca2+ extrusion by the plasma membrane Ca2+-ATPase (PMCA) is especially relevant, maintaining an elevated cytosolic free Ca2+ concentration that results in platelet hypersensitivity. Here we show that treatment of platelets from NIDDM patients with 300 U/mL catalase or 5 mM D-mannitol, which prevent H2O2- and hydroxyl radicals-mediated oxidative stress, respectively, increases Ca2+ extrusion after treatment with thapsigargin (TG) plus ionomycin (Iono). In contrast, 1 mM trolox, a scavenger of ONOO-, did not alter TG + Iono-induced response. Catalase and D-mannitol reversed the enhanced tyrosine phosphorylation of PMCA induced by TG + Iono in NIDDM patients. These findings open up new horizon for the development of therapeutic strategies to palliate cardiovascular disorders in NIDDM. FAU - Jardin, Isaac AU - Jardin I AD - Department of Physiology, University of Extremadura, 10071 Caceres, Spain. FAU - Redondo, Pedro C AU - Redondo PC FAU - Salido, Gines M AU - Salido GM FAU - Pariente, Jose A AU - Pariente JA FAU - Rosado, Juan A AU - Rosado JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Platelets JT - Platelets JID - 9208117 RN - 0 (Antioxidants) RN - 0 (Enzyme Inhibitors) RN - 0 (Ionophores) RN - 0 (Reactive Oxygen Species) RN - 21820-51-9 (Phosphotyrosine) RN - 56092-81-0 (Ionomycin) RN - 67526-95-8 (Thapsigargin) RN - EC 1.11.1.6 (Catalase) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Antioxidants/pharmacology MH - Blood Platelets/drug effects/*enzymology MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/blood/*drug effects MH - Catalase/metabolism MH - Cell Membrane/metabolism MH - Diabetes Mellitus, Type 2/*blood/enzymology MH - Enzyme Inhibitors/pharmacology MH - Humans MH - Ionomycin/pharmacology MH - Ionophores/pharmacology MH - Phosphotyrosine/analysis MH - *Platelet Activation/drug effects/physiology MH - Reactive Oxygen Species/*metabolism MH - Thapsigargin/pharmacology EDAT- 2006/08/25 09:00 MHDA- 2006/10/27 09:00 CRDT- 2006/08/25 09:00 PHST- 2006/08/25 09:00 [pubmed] PHST- 2006/10/27 09:00 [medline] PHST- 2006/08/25 09:00 [entrez] AID - U733670329825557 [pii] AID - 10.1080/09537100600745187 [doi] PST - ppublish SO - Platelets. 2006 Aug;17(5):283-8. doi: 10.1080/09537100600745187.