PMID- 23489891
OWN - NLM
STAT- MEDLINE
DCOM- 20131205
LR  - 20130520
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 37
IP  - 10
DP  - 2013 May
TI  - Protein kinase C activation causes neurite retraction via cyclinD1 and 
      p60-katanin increase in rat hippocampal neurons.
PG  - 1610-9
LID - 10.1111/ejn.12185 [doi]
AB  - Neurons are differentiated postmitotic cells residing in G0 phase of the cell 
      cycle and are unable to proceed through G1 phase, in which cyclinD1 needs to be 
      up-regulated for initiation. Yet, a growing body of evidence has shown that cell 
      cycle re-activation via cyclinD1 up-regulation drives neurons into apoptosis. By 
      contrast, there is also evidence demonstrating cell cycle proteins playing roles 
      in neuronal differentiation. cyclinD1 has been shown to be differently regulated 
      by protein kinase C alpha (PKC-alpha) in various mitotic cells. Based on these 
      different effects, we investigated the role of PKC-alpha on cyclinD1 regulation in 
      hippocampal neurons. Neurons were treated with PKC activator, PMA, and analysed 
      for subcellular distributions of PKC-alpha and cyclinD1. Remarkably, PMA treatment 
      increased nuclear PKC-alpha and cyclinD1, but not PKC-epsilon in hippocampal neurons. 
      Increases in nuclear PKC-alpha and cyclinD1 were accompanied by microtubule 
      re-organisation via increases in tau and retinoblastoma protein phosphorylation 
      levels. Increased p60-katanin and p53 changed the neuronal morphology into 
      neurons with shorter, but increased number of side branches. Since up-regulation 
      of cell cycle is associated with apoptosis in neurons, we also analysed changes 
      in Bax, Bcl-2 early and PARP (poly(ADP-ribose)polymerase), caspase3 late 
      apoptotic markers. However, we did not observe any indication of apoptosis. These 
      data suggest that in addition to their previously known roles in mitotic cells on 
      cell cycle regulation, PKC-alpha and cyclinD1 seem to be important for 
      differentiation, and nuclear PKC-alpha and cyclinD1 interfere with differentiation by 
      promoting microtubule re-organisation through PKC signaling without triggering 
      apoptosis.
CI  - (c) 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Korulu, Sirin
AU  - Korulu S
AD  - Departments of Molecular Biology and Genetics, Istanbul Technical University, 
      34469, Maslak, Istanbul, Turkey.
FAU - Yildiz-Unal, Aysegul
AU  - Yildiz-Unal A
FAU - Yuksel, Meral
AU  - Yuksel M
FAU - Karabay, Arzu
AU  - Karabay A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130315
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (tau Proteins)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Adenosine Triphosphatases/*metabolism
MH  - Animals
MH  - Apoptosis
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cyclin D1/*metabolism
MH  - Hippocampus/cytology/growth & development/*metabolism
MH  - Microtubules/ultrastructure
MH  - Neurites/*metabolism/ultrastructure
MH  - Protein Kinase C-alpha/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinoblastoma Protein/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - tau Proteins/metabolism
EDAT- 2013/03/16 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/03/16 06:00
PHST- 2012/08/07 00:00 [received]
PHST- 2013/02/11 00:00 [revised]
PHST- 2013/02/13 00:00 [accepted]
PHST- 2013/03/16 06:00 [entrez]
PHST- 2013/03/16 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1111/ejn.12185 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2013 May;37(10):1610-9. doi: 10.1111/ejn.12185. Epub 2013 Mar 15.