PMID- 23485810
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20240109
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 238
DP  - 2013 May 15
TI  - Protective effect of creatine against 6-hydroxydopamine-induced cell death in 
      human neuroblastoma SH-SY5Y cells: Involvement of intracellular signaling 
      pathways.
PG  - 185-94
LID - S0306-4522(13)00164-4 [pii]
LID - 10.1016/j.neuroscience.2013.02.030 [doi]
AB  - The guanidine-like compound creatine exerts bioenergetic, antiexcitotoxic, 
      antioxidant and neuroprotective properties; however, the intracellular mechanisms 
      responsible for these effects are still not well established. The purpose of this 
      study was to investigate the protective effect of creatine against 
      6-hydroxydopamine (6-OHDA)-induced cell death in neuroblastoma SH-SY5Y cells and 
      the possible intracellular signaling pathways involved in such effect. Exposure 
      of SH-SY5Y cells to 100-300muM of 6-OHDA for 24h caused a significant 
      concentration-dependent cell death measured as a diminution of 
      3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction and 
      as an increase in the extracellular release of lactate dehydrogenase. SH-SY5Y 
      cells incubated for 24 or 48h with creatine (10-5000muM) was not cytotoxic. 
      However, pre and co-treatment with creatine (0.3-1000muM) for 24h reduced 
      6-OHDA-induced toxicity. The protective effect afforded by creatine against 
      6-OHDA-induced toxicity was reversed by inhibitors of different protein kinases, 
      i.e. phosphatidylinositol-3 kinase (PI3K) (LY294002), Ca(2+)/calmodulin-dependent 
      protein kinase II (CaMKII) (KN-93), protein kinase A (H-89), mitogen-activated 
      protein kinase kinase 1/2 (MEK1/2) (PD98059) and protein kinase C (PKC) 
      (chelerythrine). Furthermore, creatine prevented the 6-OHDA-induced 
      dephosphorylation of glycogen synthase kinase-3beta (GSK-3beta) at the serine 9 
      residue. In conclusion, the results of this study show that creatine can protect 
      against 6-OHDA-induced toxicity and its protective mechanism is related to a 
      signaling pathway that involves PI3K, PKC, PKA, CaMKII, MEK1/2 and GSK-3beta.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Cunha, M P
AU  - Cunha MP
AD  - Instituto Teofilo Hernando, Facultad de Medicina, Universidad Autonoma de Madrid, 
      4-28029 Madrid, Spain. mauricio.personal@gmail.com
FAU - Martin-de-Saavedra, M D
AU  - Martin-de-Saavedra MD
FAU - Romero, A
AU  - Romero A
FAU - Parada, E
AU  - Parada E
FAU - Egea, J
AU  - Egea J
FAU - Del Barrio, L
AU  - Del Barrio L
FAU - Rodrigues, A L S
AU  - Rodrigues AL
FAU - Lopez, M G
AU  - Lopez MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130226
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Creatine/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Neuroblastoma/metabolism/*pathology
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Oxidopamine/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/*drug effects
EDAT- 2013/03/15 06:00
MHDA- 2013/10/18 06:00
CRDT- 2013/03/15 06:00
PHST- 2012/09/24 00:00 [received]
PHST- 2013/02/15 00:00 [revised]
PHST- 2013/02/15 00:00 [accepted]
PHST- 2013/03/15 06:00 [entrez]
PHST- 2013/03/15 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
AID - S0306-4522(13)00164-4 [pii]
AID - 10.1016/j.neuroscience.2013.02.030 [doi]
PST - ppublish
SO  - Neuroscience. 2013 May 15;238:185-94. doi: 10.1016/j.neuroscience.2013.02.030. 
      Epub 2013 Feb 26.