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Homocysteine induces caspase activation by endoplasmic reticulum stress in platelets from type 2 diabetics and healthy donors
- Source :
- Thrombosis and Haemostasis. 103:1022-1032
- Publication Year :
- 2010
- Publisher :
- Georg Thieme Verlag KG, 2010.
-
Abstract
- SummaryDiabetes mellitus is a disease characterised by hyperglycaemia and associated with several cardiovascular disorders, including angiopathy and platelet hyperactivity, which are major causes of morbidity and mortality in type 2 diabetes mellitus. In type 2 diabetic patients, homo-cysteine levels are significantly increased compared with healthy subjects. Hyperhomocysteinaemia is an independent risk factor for macro-and microangiopathy and mortality. The present study is aimed to investigate the effect of homocysteine on platelet apoptosis. Changes in cytosolic or intraluminal free Ca2+ concentration were determined by fluorimetry. Caspase activity and phosphorylation of the eukaryotic initiation factor 2α (eIF2α) were explored by Western blot. Our results indicate that homocysteine releases Ca2+ from agonist sensitive stores, enhances eIF2α phosphorylation at Ser51 and activates caspase-3 and -9 independently of extracellular Ca2+. Homocysteine induced activation of caspase-3 and -9 was abolished by salubrinal, an agent that prevents endoplasmic reticulum (ER) stress-induced apoptosis. Homo-cysteine-induced platelet effects were significantly greater in type 2 diabetics than in healthy subjects. These findings demonstrate that homocysteine induces ER stress-mediated apoptosis in human platelets, an event that is enhanced in type 2 diabetic patients, which might be involved in the pathogenesis of cardiovascular complications associated with type 2 diabetes mellitus.
- Subjects :
- Blood Platelets
medicine.medical_specialty
Homocysteine
Hyperhomocysteinemia
Apoptosis
Blood Donors
Type 2 diabetes
Biology
Endoplasmic Reticulum
Angiopathy
Salubrinal
eIF-2 Kinase
chemistry.chemical_compound
Stress, Physiological
Internal medicine
Diabetes mellitus
medicine
Humans
Calcium Signaling
Cells, Cultured
Caspase 3
Endoplasmic reticulum
Microangiopathy
Thiourea
Type 2 Diabetes Mellitus
Hematology
medicine.disease
Caspase 9
Enzyme Activation
Endocrinology
Diabetes Mellitus, Type 2
chemistry
Cinnamates
Diabetic Angiopathies
Subjects
Details
- ISSN :
- 2567689X and 03406245
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....0e660182abca173ae3b9c130371b6375