PMID- 25239763
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1843
IP  - 12
DP  - 2014 Dec
TI  - Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor 
      inhibit ferrous iron influx via divalent metal transporter 1 and iron regulatory 
      protein 1 regulation in ventral mesencephalic neurons.
PG  - 2967-75
LID - S0167-4889(14)00335-8 [pii]
LID - 10.1016/j.bbamcr.2014.09.010 [doi]
AB  - Iron accumulation is observed in the substantia nigra of patients with 
      Parkinson's disease. However, it is unknown whether neurotrophic factors, 
      brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic 
      factor (GDNF) participate in the modulation of neuronal iron metabolism. Here, we 
      investigated the effects and underlying mechanisms of BDNF and GDNF on the iron 
      influx process in primary cultured ventral mesencephalic neurons. 
      6-hydroxydopamine-induced enhanced ferrous iron influx via improper up-regulation 
      of divalent metal transporter 1 with iron responsive element (DMT1+IRE) was 
      consistently relieved by BDNF and GDNF. Both the mRNA and protein levels of 
      DMT1+IRE were down-regulated by BDNF or GDNF treatment alone. We further 
      demonstrated the involvement of iron regulatory protein 1 (IRP1) in BDNF- and 
      GDNF-induced DMT1+IRE expression. Extracellular-regulated kinase 1/2 (ERK1/2) and 
      Akt were activated and participated in these processes. Inhibition of ERK1/2 and 
      Akt phosphorylation abolished the down-regulation of IRP1 and DMT1+IRE induced by 
      BDNF and GDNF. Taken together, these results show that BDNF and GDNF ameliorate 
      iron accumulation via the ERK/Akt pathway, followed by inhibition of IRP1 and 
      DMT1+IRE expression, which may provide new targets for the neuroprotective 
      effects of these neurotrophic factors.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Zhang, Hao-Yun
AU  - Zhang HY
AD  - Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and 
      Prevention of Neurological Disorders and State Key Disciplines, Medical College 
      of Qingdao University, Qingdao 266071, China; Shandong Provincial Collaborative 
      Innovation Center for Neurodegenerative Disorders, PR China; Department of 
      Histology and Embryology, Shandong Provincial Key Laboratory of Human Anatomy and 
      Embryology, Weifang Medical University, Weifang 261053, China.
FAU - Song, Ning
AU  - Song N
AD  - Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and 
      Prevention of Neurological Disorders and State Key Disciplines, Medical College 
      of Qingdao University, Qingdao 266071, China; Shandong Provincial Collaborative 
      Innovation Center for Neurodegenerative Disorders, PR China.
FAU - Jiang, Hong
AU  - Jiang H
AD  - Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and 
      Prevention of Neurological Disorders and State Key Disciplines, Medical College 
      of Qingdao University, Qingdao 266071, China; Shandong Provincial Collaborative 
      Innovation Center for Neurodegenerative Disorders, PR China.
FAU - Bi, Ming-Xia
AU  - Bi MX
AD  - Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and 
      Prevention of Neurological Disorders and State Key Disciplines, Medical College 
      of Qingdao University, Qingdao 266071, China; Shandong Provincial Collaborative 
      Innovation Center for Neurodegenerative Disorders, PR China.
FAU - Xie, Jun-Xia
AU  - Xie JX
AD  - Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and 
      Prevention of Neurological Disorders and State Key Disciplines, Medical College 
      of Qingdao University, Qingdao 266071, China; Shandong Provincial Collaborative 
      Innovation Center for Neurodegenerative Disorders, PR China. Electronic address: 
      jxiaxie@public.qd.sd.cn.
LA  - eng
PT  - Journal Article
DEP - 20140916
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
SB  - IM
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Divalent metal transporter 1 with iron responsive element
OT  - Glial cell line-derived neurotrophic factor
OT  - Iron regulatory protein 1
OT  - Parkinson's disease
EDAT- 2014/09/23 06:00
MHDA- 2014/09/23 06:01
CRDT- 2014/09/21 06:00
PHST- 2014/04/19 00:00 [received]
PHST- 2014/08/26 00:00 [revised]
PHST- 2014/09/09 00:00 [accepted]
PHST- 2014/09/21 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2014/09/23 06:01 [medline]
AID - S0167-4889(14)00335-8 [pii]
AID - 10.1016/j.bbamcr.2014.09.010 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2014 Dec;1843(12):2967-75. doi: 
      10.1016/j.bbamcr.2014.09.010. Epub 2014 Sep 16.