PMID- 24456637
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20151119
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 263
DP  - 2014 Mar 28
TI  - Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects 
      native and amyloid-precursor-protein-transfected neuroblastoma cells against 
      oxidative stress-induced death.
PG  - 203-15
LID - S0306-4522(14)00030-X [pii]
LID - 10.1016/j.neuroscience.2013.12.067 [doi]
AB  - Clinical observations suggested that gamma-hydroxybutyrate (GHB) protects nerve 
      cells against death but the direct proofs are missing. Here, we combined several 
      approaches to investigate GHB capacity to protect human neuroblastoma SH-SY5Y 
      cells against hydrogen peroxide (H2O2)-induced death. To increase the 
      patho-physiological relevancy of our study, we used native SH-SY5Y cells and 
      SH-SY5Y cells stably transfected with the wild-type amyloid-precursor-protein 
      (APPwt) or control-vector-pCEP4. Trypan Blue exclusion and MTT 
      (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium-bromide) assays combined 
      with pharmacological analyses showed that H2O2 reduced native and genetically 
      modified cell viability and APPwt-transfected cells were the most vulnerable. 
      Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and 
      activated caspase-3 staining assessed by flow cytometry revealed a basally 
      elevated apoptotic signal in APPwt-transfected cells. Reverse-transcription, 
      real-time quantitative polymerase chain reaction (qPCR) and Western blotting 
      showed that mRNA and protein basal ratios of apoptotic modulators Bax/Bcl-2 were 
      also high in APPwt-transfected cells. GHB efficiently and dose-dependently 
      rescued native and genetically modified cells from H2O2-induced death. 
      Interestingly, GHB, which strongly decreased elevated basal levels of 
      TUNEL-staining, activated caspase 3-labeling and Bax/Bcl-2 in APPwt-transfected 
      cells, also counteracted H2O2-evoked increased apoptotic markers in native and 
      genetically modified SH-SY5Y cells. Since GHB did not promote cell proliferation, 
      anti-apoptotic action through the down-regulation of Bax/Bcl-2 ratios and/or 
      caspase 3 activity appears as a critical mechanism involved in GHB-induced 
      protection of SH-SY5Y cells against APPwt-overexpression- or H2O2-evoked death. 
      Altogether, these results, providing multi-parametric evidence for the existence 
      of neuroprotective action of GHB, also open interesting perspectives for the 
      development of GHB analog-based strategies against neurodegeneration or nerve 
      cell death.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Wendt, G
AU  - Wendt G
AD  - Biopathologie de la Myeline, Neuroprotection et Strategies Therapeutiques, INSERM 
      U1119, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite 
      de Strasbourg, Batiment 3 de la Faculte de Medecine, 11 rue Humann, 67 000 
      Strasbourg, France; Molekular- und Zellbiologie, Zentrum fur Human- und 
      Molekularbiologie (ZHMB), Universitat des Saarlandes, Campus A 1.5, D-66041 
      Saarbrucken, Germany.
FAU - Kemmel, V
AU  - Kemmel V
AD  - Biopathologie de la Myeline, Neuroprotection et Strategies Therapeutiques, INSERM 
      U1119, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite 
      de Strasbourg, Batiment 3 de la Faculte de Medecine, 11 rue Humann, 67 000 
      Strasbourg, France.
FAU - Patte-Mensah, C
AU  - Patte-Mensah C
AD  - Biopathologie de la Myeline, Neuroprotection et Strategies Therapeutiques, INSERM 
      U1119, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite 
      de Strasbourg, Batiment 3 de la Faculte de Medecine, 11 rue Humann, 67 000 
      Strasbourg, France.
FAU - Uring-Lambert, B
AU  - Uring-Lambert B
AD  - Laboratoire d'Immunologie et d'Hematologie, Hopitaux Universitaires de 
      Strasbourg, 1 Place de l'Hopital, 67 000 Strasbourg, France.
FAU - Eckert, A
AU  - Eckert A
AD  - Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University 
      Clinic, Wilhelm Klein-Strasse 27, CH-4025 Basel, Switzerland.
FAU - Schmitt, M J
AU  - Schmitt MJ
AD  - Molekular- und Zellbiologie, Zentrum fur Human- und Molekularbiologie (ZHMB), 
      Universitat des Saarlandes, Campus A 1.5, D-66041 Saarbrucken, Germany.
FAU - Mensah-Nyagan, A G
AU  - Mensah-Nyagan AG
AD  - Biopathologie de la Myeline, Neuroprotection et Strategies Therapeutiques, INSERM 
      U1119, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite 
      de Strasbourg, Batiment 3 de la Faculte de Medecine, 11 rue Humann, 67 000 
      Strasbourg, France. Electronic address: gmensah@unistra.fr.
LA  - eng
PT  - Journal Article
DEP - 20140120
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Neuroprotective Agents)
RN  - 7G33012534 (Sodium Oxybate)
SB  - IM
MH  - Amyloid beta-Protein Precursor/genetics/*metabolism
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Humans
MH  - Neuroblastoma
MH  - Neuroprotective Agents/*pharmacology
MH  - *Oxidative Stress
MH  - Sodium Oxybate/*pharmacology
MH  - Transfection
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - anti-apoptotic drug
OT  - anti-oxidant drug
OT  - mechanisms of action of GHB
OT  - neuroprotection
EDAT- 2014/01/25 06:00
MHDA- 2014/11/02 06:00
CRDT- 2014/01/25 06:00
PHST- 2012/11/09 00:00 [received]
PHST- 2013/12/20 00:00 [revised]
PHST- 2013/12/27 00:00 [accepted]
PHST- 2014/01/25 06:00 [entrez]
PHST- 2014/01/25 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
AID - S0306-4522(14)00030-X [pii]
AID - 10.1016/j.neuroscience.2013.12.067 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Mar 28;263:203-15. doi: 10.1016/j.neuroscience.2013.12.067. 
      Epub 2014 Jan 20.