PMID- 27114559
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20211204
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 473
IP  - 13
DP  - 2016 Jul 1
TI  - GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat 
      cerebellar granule neurons.
PG  - 1895-904
LID - 10.1042/BCJ20160362 [doi]
AB  - GDF-15 (growth/differentiation factor 15) is a novel member of the TGF 
      (transforming growth factor)-beta superfamily that has critical roles in the central 
      and peripheral nervous systems. We reported previously that GDF-15 increased 
      delayed rectifier outward K(+) currents and Kv2.1 alpha subunit expression through 
      TbetaRII (TGF-beta receptor II) to activate Src kinase and Akt/mTOR (mammalian target 
      of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present 
      study, we found that treatment of CGNs with GDF-15 for 24 h increased the 
      intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane 
      depolarization, as determined by Ca(2+) imaging. Whole-cell current recordings 
      indicated that GDF-15 increased the inward Ca(2+) current (ICa) without altering 
      steady-state activation of Ca(2+) channels. Treatment with nifedipine, an 
      inhibitor of L-type Ca(2+) channels, abrogated GDF-15-induced increases in 
      [Ca(2+)]i and ICa The GDF-15-induced increase in ICa was mediated via 
      up-regulation of the Cav1.3 alpha subunit, which was attenuated by inhibiting 
      Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by 
      pharmacological inhibition of Src-mediated TbetaRII phosphorylation. Given that 
      Cav1.3 is not only a channel for Ca(2+) influx, but also a transcriptional 
      regulator, our data confirm that GDF-15 induces protein expression via TbetaRII and 
      activation of a non-Smad pathway, and provide novel insight into the mechanism of 
      GDF-15 function in neurons.
CI  - (c) 2016 The Author(s).
FAU - Lu, Jun-Mei
AU  - Lu JM
AD  - Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and 
      School of Life Sciences, Fudan University, Shanghai 200433, China.
FAU - Wang, Chang-Ying
AU  - Wang CY
AD  - Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and 
      School of Life Sciences, Fudan University, Shanghai 200433, China.
FAU - Hu, Changlong
AU  - Hu C
AD  - Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and 
      School of Life Sciences, Fudan University, Shanghai 200433, China.
FAU - Fang, Yan-Jia
AU  - Fang YJ
AD  - Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and 
      School of Life Sciences, Fudan University, Shanghai 200433, China 
      081023023@fudan.edu.cn yamei@fudan.edu.cn.
FAU - Mei, Yan-Ai
AU  - Mei YA
AD  - Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and 
      School of Life Sciences, Fudan University, Shanghai 200433, China 
      081023023@fudan.edu.cn yamei@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160425
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Growth Differentiation Factor 15)
RN  - 166872-16-8 (Cacna1d protein, rat)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/*metabolism
MH  - Cells, Cultured
MH  - Cerebellum/*cytology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Growth Differentiation Factor 15/*pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - Nifedipine/pharmacology
MH  - Oncogene Protein v-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4925162
OTO - NOTNLM
OT  - Akt/mTOR
OT  - Cav1.3
OT  - ERK
OT  - GDF-15
OT  - TbetaRII
OT  - [Ca2+]i
EDAT- 2016/04/27 06:00
MHDA- 2017/05/16 06:00
PMCR- 2016/06/28
CRDT- 2016/04/27 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/04/27 06:00 [entrez]
PHST- 2016/04/27 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2016/06/28 00:00 [pmc-release]
AID - BCJ20160362 [pii]
AID - 10.1042/BCJ20160362 [doi]
PST - ppublish
SO  - Biochem J. 2016 Jul 1;473(13):1895-904. doi: 10.1042/BCJ20160362. Epub 2016 Apr 
      25.