PMID- 16481105
OWN - NLM
STAT- MEDLINE
DCOM- 20060630
LR  - 20131121
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 399
IP  - 1-2
DP  - 2006 May 15
TI  - Effects of SDF-1alpha and gp120IIIB on apoptotic pathways in SK-N-SH 
      neuroblastoma cells.
PG  - 115-20
AB  - CXCR4, a chemokine receptor constitutively expressed in the brain, binds both 
      ligands, the chemokine SDF-1alpha and the HIV envelope glycoprotein gp120(IIIB). 
      There seem to be intracellular differences between the neuronal apoptosis induced 
      by SDF-1alpha and that induced by gp120(IIIB), but the apoptotic pathways 
      involved have not been compared in human neuronal cells. In this study, we 
      characterized the apoptotic intracellular pathways activated by neurotoxic 
      concentrations of SDF-1alpha and gp120(IIIB) in human neuroblastoma cells 
      SK-N-SH. SDF-1alpha (10 nM) and gp120(IIIB) (2 nM) induced similar levels of 
      apoptosis after 24 h of incubation (49 +/- 4% and 48 +/- 3%, respectively, of the 
      neurons were apoptotic). SDF1alpha-induced apoptosis was completely abolished by 
      the inhibition of Src phosphorylation by PP2. Exposure to SDF-1alpha (10 nM) 
      triggered an increase in Src phosphorylation, with a maximum after 20 min of 
      incubation (1.80 +/- 0.24 times higher than control, P = 0.01). NMDA calcium flux 
      was enhanced only if cells were incubated with SDF-1alpha for 20 min before 
      applying NMDA. By contrast, gp120(IIIB)-induced apoptosis was not affected by the 
      inhibition of Src phosphorylation. Moreover, gp120(IIIB) enhanced NMDA calcium 
      flux immediately, without modifying Src phosphorylation status. Finally, levels 
      of phospho-JNK increased following exposure to gp120(IIIB) (by a factor of 1.46 
      +/- 0.4 at 120 min, P = 0.03), but not after exposure to SDF-1alpha. Thus, 
      SDF-1alpha and gp120(IIIB) induced a similar level of neuronal apoptosis, but by 
      activating different intracellular pathways. SDF-1alpha enhanced NMDA activity 
      indirectly via Src phosphorylation, whereas gp120(IIIB) probably activated the 
      NMDA receptor directly and phosphorylated JNK.
FAU - Geeraerts, Thomas
AU  - Geeraerts T
AD  - Laboratoire Immunologie antivirale systemique et cerebrale, INSERM EMI 0109, 
      Faculte de medecine Paris-Sud, 63 rue Gabriel Peri, 94 276 Le Kremlin Bicetre, 
      France. thgeeraerts@hotmail.com
FAU - Deiva, Kumaran
AU  - Deiva K
FAU - M'sika, Ilana
AU  - M'sika I
FAU - Salim, Hassan
AU  - Salim H
FAU - Hery, Christiane
AU  - Hery C
FAU - Tardieu, Marc
AU  - Tardieu M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060214
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Apoptosis
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/*physiology/toxicity
MH  - HIV Envelope Protein gp120/pharmacology/*physiology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Intracellular Space/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - N-Methylaspartate/pharmacology
MH  - Neuroblastoma
MH  - Phosphorylation
MH  - Receptors, CXCR4/biosynthesis
MH  - Receptors, N-Methyl-D-Aspartate/agonists
MH  - src-Family Kinases/metabolism
EDAT- 2006/02/17 09:00
MHDA- 2006/07/01 09:00
CRDT- 2006/02/17 09:00
PHST- 2005/10/28 00:00 [received]
PHST- 2006/01/10 00:00 [revised]
PHST- 2006/01/18 00:00 [accepted]
PHST- 2006/02/17 09:00 [pubmed]
PHST- 2006/07/01 09:00 [medline]
PHST- 2006/02/17 09:00 [entrez]
AID - S0304-3940(06)00071-1 [pii]
AID - 10.1016/j.neulet.2006.01.033 [doi]
PST - ppublish
SO  - Neurosci Lett. 2006 May 15;399(1-2):115-20. doi: 10.1016/j.neulet.2006.01.033. 
      Epub 2006 Feb 14.