Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation

Cardiovascular Diabetology

Original Investigation

Hirohito Sone¹  Osamu Hanyu¹  Hidekazu Sotoyama²  Hiroyuki Nawa²  Yuriko Iwakura²  Nobuyuki Takei²  Kazuo Furukawa³  Ichiro Fuse⁴ 

[1] Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan;Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Asahimachi, 951-8585, Niigata, Japan;Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Asahimachi, 951-8585, Niigata, Japan;Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan;Japanese Red Cross Niigata Blood Center, Niigata, Japan;

关键词: AGE;    BDNF;    Platelets;    Release;    Ca;    Src family kinases;    Syk;   

DOI  :  10.1186/s12933-017-0505-y

 received in 2016-11-29, accepted in 2017-02-03,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBrain-derived neurotrophic factor (BDNF) exerts beneficial effects not only on diabetic neuropathies but also on cardiovascular injury. There is argument regarding the levels of serum BDNF in patients with diabetes mellitus (DM). Because BDNF in peripheral blood is rich in platelets, this may represent dysregulation of BDNF release from platelets. Here we focused on advanced glycation end products (AGEs), which are elevated in patients with DM and have adverse effects on cardiovascular functions. The aim of this study is to elucidate the role of AGEs in the regulation of BDNF release from human platelets.MethodsPlatelets collected from peripheral blood of healthy volunteers were incubated with various concentrations of AGE (glycated-BSA) at 37 °C for 5 min with or without BAPTA-AM, a cell permeable Ca2+ chelator, or PP2, a potent inhibitor of Src family kinases (SFKs). Released and cellular BDNF were measured by ELISA and calculated. Phosphorylation of Src and Syk, a downstream kinase of SFKs, in stimulated platelets was examined by Western blotting and immunoprecipitation.ResultsAGE induced BDNF release from human platelets in a dose-dependent manner, which was dependent on intracellular Ca2+ and SFKs. We found that AGE induced phosphorylation of Src and Syk.ConclusionsAGE induces BDNF release from human platelets through the activation of the Src-Syk-(possibly phospholipase C)-Ca2+ pathway. Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of DM.

【 授权许可】

CC BY   
© The Author(s) 2017