【博士論文】学術データベース

博士論文 / Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation 最終糖化産物(AGEs)はヒト血小板において、Srcファミリーキナーゼの活性化を介して脳由来神経栄養因子(BDNF)の放出を促進させる

著者

書誌事項

タイトル

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

タイトル別名

最終糖化産物(AGEs)はヒト血小板において、Srcファミリーキナーゼの活性化を介して脳由来神経栄養因子(BDNF)の放出を促進させる

著者名

Furukawa Kazuo

著者名

古川和郎

学位授与大学

新潟大学 (大学ID:0035) (CAT機関ID:KI000356)

取得学位

博士(医学)

学位授与番号

甲第4357号

学位授与年月日

2017-09-20

注記・抄録

学位の種類: 博士(医学). 報告番号: 甲第4357号. 学位記番号: 新大院博(医)甲第770号. 学位授与年月日: 平成29年9月20日

Cardiovascular Diabetology. 2017, 16, 20.

Background: Brain-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. Methods: Platelets 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 Ca^<2+> 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. Results: AGE induced BDNF release from human platelets in a dose-dependent manner, which was dependent on intracellular Ca^<2+> and SFKs. We found that AGE induced phosphorylation of Src and Syk. Conclusions: AGE induces BDNF release from human platelets through the activation of the Src-Syk-(possibly phospholipase C)-Ca^<2+> 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.

元資料の権利情報 : (C) The Author(s) 2017

キーワード

platelets, age, Ca^<2+>, Src family kinases, BDNF, Release, Syk

各種コード

NII論文ID(NAID)

500001044119

NII著者ID(NRID)
  • 8000001153893
  • 8000001153894
DOI (出版社)

10.1186/s12933-017-0505-y

DOI

info:doi/10.1186/s12933-017-0505-y

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

外部リンク

DOI

博士論文 / 新潟大学 / 医学

博士論文 / 新潟大学

博士論文 / 医学

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