Abstract
Platelet hyperaggregability might contribute to vascular complications associated with type 2 diabetes mellitus (DM2).Experimental evidence supports a direct link between altered Ca2+ entry and hyperaggregability in DM2 patients. Objectives: We aimed to investigate whether altered immunophilin expression and function are involved in the abnormal Ca2+ entry observed in platelets from DM2 patients. Results: Inhibition of immunophilins by tacrolimus (FK506) and sirolimus (rapamycin) reduced Ca2+ entry in platelets from healthy donors and DM2 patients. Similarly, immunophilin inhibitors reduced platelet degranulation in both healthy and DM2 subjects. Nevertheless, α-granule secretion reduction was greater than that observed for dense granules in platelets from DM2 patients. However, no difference was observed in the inhibition of secretion in platelets from healthy subjects. Additionally, altered expression of FK506 binding protein-52 (FKBP52) and coupling to Ca2+ channels were found in platelets from DM2 patients compared to healthy subjects. Finally, reduction in platelet function from healthy subjects and DM2 patients in the presence of immunophilin antagonists was observed, being this dysfunction more evident in platelets from DM2 patients. Conclusions: We suggest that, among others, FKBP52 expression and function are altered in platelets from DM2 patients, contributing to the altered Ca2+ entry and hyperaggregability in these cells.
Keywords: Aggregation, DM2, FKBP52, immunophilin, secretion, SOCE.
Current Medicinal Chemistry
Title:Immunophilins are Involved in the Altered Platelet Aggregation Observed in Patients with Type 2 Diabetes Mellitus
Volume: 20 Issue: 14
Author(s): E. Lopez, A. Berna- Erro, J.M. Hernandez-Cruz, G.M. Salido, P.C. Redondo and J.A. Rosado
Affiliation:
Keywords: Aggregation, DM2, FKBP52, immunophilin, secretion, SOCE.
Abstract: Platelet hyperaggregability might contribute to vascular complications associated with type 2 diabetes mellitus (DM2).Experimental evidence supports a direct link between altered Ca2+ entry and hyperaggregability in DM2 patients. Objectives: We aimed to investigate whether altered immunophilin expression and function are involved in the abnormal Ca2+ entry observed in platelets from DM2 patients. Results: Inhibition of immunophilins by tacrolimus (FK506) and sirolimus (rapamycin) reduced Ca2+ entry in platelets from healthy donors and DM2 patients. Similarly, immunophilin inhibitors reduced platelet degranulation in both healthy and DM2 subjects. Nevertheless, α-granule secretion reduction was greater than that observed for dense granules in platelets from DM2 patients. However, no difference was observed in the inhibition of secretion in platelets from healthy subjects. Additionally, altered expression of FK506 binding protein-52 (FKBP52) and coupling to Ca2+ channels were found in platelets from DM2 patients compared to healthy subjects. Finally, reduction in platelet function from healthy subjects and DM2 patients in the presence of immunophilin antagonists was observed, being this dysfunction more evident in platelets from DM2 patients. Conclusions: We suggest that, among others, FKBP52 expression and function are altered in platelets from DM2 patients, contributing to the altered Ca2+ entry and hyperaggregability in these cells.
Export Options
About this article
Cite this article as:
Lopez E., Erro Berna- A., Hernandez-Cruz J.M., Salido G.M., Redondo P.C. and Rosado J.A., Immunophilins are Involved in the Altered Platelet Aggregation Observed in Patients with Type 2 Diabetes Mellitus, Current Medicinal Chemistry 2013; 20 (14) . https://dx.doi.org/10.2174/0929867311320140008
DOI https://dx.doi.org/10.2174/0929867311320140008 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Current View from Alzheimer Disease to Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets CCR1 and CCR2 Antagonists
Current Topics in Medicinal Chemistry Adenosine Myocardial Perfusion Imaging
Current Medical Imaging Cardiovascular-Active Venom Toxins: An Overview
Current Medicinal Chemistry Unfolded Protein Response as a Therapeutic Target in Cardiovascular Disease
Current Topics in Medicinal Chemistry Synthesis of Iminosugars from Tetroses
Current Organic Synthesis Age Related Macular Degeneration and Visual Disability
Current Drug Targets Phenomenology and Neurobiology of Childhood Onset Schizophrenia
Current Psychiatry Reviews Recent Advances in the Treatment of Neurogenic Erectile Dysfunction
Recent Patents on CNS Drug Discovery (Discontinued) Objectively Assessed Physical Activity and Sedentary Behaviour During Pregnancy in Portuguese Women: Differences Between Trimesters and Weekdays and Weekends
Current Women`s Health Reviews Therapeutic Strategies Targeting Endothelial Function in Humans:Clinical Implications
Current Vascular Pharmacology Catheter Ablation of Lone Atrial Fibrillation
Current Pharmaceutical Design Should Cushing's Syndrome be Considered as a Disease with High Cardiovascular Risk in Relevant Guidelines?
Current Vascular Pharmacology Comparison of Artemisia annua Bioactivities between Traditional Medicine and Chemical Extracts
Current Bioactive Compounds Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism
Current Pharmaceutical Design Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction
Current Pharmaceutical Biotechnology Natural Agents Modulating ACE-2: A Review of Compounds with Potential against SARS-CoV-2 Infections
Current Pharmaceutical Design Formulation and Characterization of Gliclazide Oral Dissolving Films
Drug Delivery Letters Nanofibers: New Insights for Drug Delivery and Tissue Engineering
Current Topics in Medicinal Chemistry Mechanisms of Diabetic Dyslipidemia: Relevance for Atherogenesis
Current Vascular Pharmacology