Higher mitochondrial potential and elevated mitochondrial respiration are associated with excessive activation of blood platelets in diabetic rats

作者：Siewiera Karolina^*; Kassassir Hassan; Talar Marcin; Wieteska Lukasz; Watala Cezary

来源：Life Sciences, 2016, 148: 293-304.

DOI：10.1016/j.lfs.2016.02.030

• Blood platelets
• Diabetes mellitus
• Mitochondrial respiration
• Mitochondrial membrane potential
• Platelet activation and reactivity

Aims: The high glucose concentration observed in diabetic patients is a recognized factor of mitochondrial damage in various cell types. Its impact onmitochondrial bioenergetics in blood platelets remains largely vague. The aim of the study was to determine how the metabolism of carbohydrates, which has been impaired by streptozotocin-induced diabetes may affect the functioning of platelet mitochondria.
Materials and methods: Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Plateletmitochondrial respiratory capacitywas monitored as oxygen consumption (high-resolution respirometry). Mitochondrial membrane potential was assessed using a fluorescent probe, JC-1. Activation of circulating platelets was monitored by flow cytometry measuring of the expressions of CD61 and CD62P on a blood platelet surface. To determine mitochondrial protein density in platelets, Western Blot technique was used.
Key findings: The results indicate significantly elevated mitochondria mass, increased mitochondrial membrane potential (Delta psi m) and enhanced respiration in STZ-diabetic animals, although the respiration control ratios appear to remain unchanged. Higher Delta psi m and elevated mitochondrial respiration were closely related to the excessive activation of circulating platelets in diabetic animals.
Significance: Long-termdiabetes can result in increasedmitochondrial mass andmay lead to hyperpolarization of blood platelet mitochondrial membrane. These alterations may be a potential underlying cause of abnormal platelet functioning in diabetes mellitus and hence, a potential target for antiplatelet therapies in diabetes.

• 出版日期2016-3-1