PMID- 28178976
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20181202
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Feb 8
TI  - Advanced glycation end products induce brain-derived neurotrophic factor release 
      from human platelets through the Src-family kinase activation.
PG  - 20
LID - 10.1186/s12933-017-0505-y [doi]
LID - 20
AB  - 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  degrees 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.
FAU - Furukawa, Kazuo
AU  - Furukawa K
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi, Niigata, 951-8585, Japan.
AD  - Department of Hematology, Endocrinology and Metabolism, Niigata University 
      Faculty of Medicine, Niigata, Japan.
FAU - Fuse, Ichiro
AU  - Fuse I
AD  - Japanese Red Cross Niigata Blood Center, Niigata, Japan.
FAU - Iwakura, Yuriko
AU  - Iwakura Y
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi, Niigata, 951-8585, Japan.
FAU - Sotoyama, Hidekazu
AU  - Sotoyama H
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi, Niigata, 951-8585, Japan.
FAU - Hanyu, Osamu
AU  - Hanyu O
AD  - Department of Hematology, Endocrinology and Metabolism, Niigata University 
      Faculty of Medicine, Niigata, Japan.
FAU - Nawa, Hiroyuki
AU  - Nawa H
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi, Niigata, 951-8585, Japan.
FAU - Sone, Hirohito
AU  - Sone H
AD  - Department of Hematology, Endocrinology and Metabolism, Niigata University 
      Faculty of Medicine, Niigata, Japan.
FAU - Takei, Nobuyuki
AU  - Takei N
AUID- ORCID: 0000-0002-6122-939X
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi, Niigata, 951-8585, Japan. nobtak@bri.niigata-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170208
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glycation End Products, Advanced)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Blood Platelets/*drug effects/enzymology/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Humans
MH  - Middle Aged
MH  - Phosphorylation
MH  - Serum Albumin, Bovine/*pharmacology
MH  - Syk Kinase/metabolism
MH  - Type C Phospholipases/metabolism
MH  - src-Family Kinases/*metabolism
PMC - PMC5299653
OTO - NOTNLM
OT  - AGE
OT  - BDNF
OT  - Ca2+
OT  - Platelets
OT  - Release
OT  - Src family kinases
OT  - Syk
EDAT- 2017/02/10 06:00
MHDA- 2017/10/17 06:00
PMCR- 2017/02/08
CRDT- 2017/02/10 06:00
PHST- 2016/11/29 00:00 [received]
PHST- 2017/02/03 00:00 [accepted]
PHST- 2017/02/10 06:00 [entrez]
PHST- 2017/02/10 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
PHST- 2017/02/08 00:00 [pmc-release]
AID - 10.1186/s12933-017-0505-y [pii]
AID - 505 [pii]
AID - 10.1186/s12933-017-0505-y [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2017 Feb 8;16(1):20. doi: 10.1186/s12933-017-0505-y.