PMID- 19303913
OWN - NLM
STAT- MEDLINE
DCOM- 20090921
LR  - 20191210
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 161
IP  - 1
DP  - 2009 Jun 16
TI  - Phosphorylation of FADD (Fas-associated death domain protein) at serine 194 is 
      increased in the prefrontal cortex of opiate abusers: relation to mitogen 
      activated protein kinase, phosphoprotein enriched in astrocytes of 15 kDa, and 
      Akt signaling pathways involved in neuroplasticity.
PG  - 23-38
LID - 10.1016/j.neuroscience.2009.03.028 [doi]
AB  - Fas-associated protein with death domain (FADD) is a multifunctional protein that 
      can induce both apoptotic and non-apoptotic actions. Recently, FADD was found 
      downregulated in the prefrontal cortex of opiate abusers, which suggested an 
      attenuation of Fas death signals in human addicts. Phosphorylation of FADD 
      (Ser194) has been reported to regulate its non-apoptotic activity, which might 
      include the induction of neuroplastic effects in the brain. This postmortem brain 
      study examined the status of phosphorylated (p)-Ser194 FADD and signaling 
      pathways involved in neuroplasticity in the prefrontal cortex (BA 9) of 
      short-term (ST) and long-term (LT) heroin or methadone abusers. In these 
      subjects, the content of monomeric p-FADD was significantly increased when 
      compared with that in age-, gender-, and postmortem delay-matched controls (all 
      addicts: 65%, n=26; ST abuse: 51%; n=11; LT abuse: 75%, n=15). Oligomeric p-FADD 
      forms were modestly increased (11%-23%). At the subcellular level, opiate 
      addiction upregulated the expression of monomeric p-FADD in the nucleus (110%) 
      and that of p-oligomers in the cytosol (66%). In LT opiate addicts (but not ST 
      abusers), a pronounced downregulation of p-extracellular signal-regulated kinase 
      (ERK)1/2 (52%) and p-c-Jun NH(2)-terminal protein kinase (JNK)1/2 (51%), but not 
      p-p38 mitogen-activated protein kinase (MAPK), was quantified in the prefrontal 
      cortex (total homogenate and subcellular compartments). Similarly, the signaling 
      pathway mediated by p-phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) 
      protein and its phosphorylating kinase p-Akt1 was also downregulated in cortical 
      homogenate (43% and 41%, respectively) and cytosolic preparations of chronic 
      opiate addicts. The results indicate that opiate addiction in humans is 
      associated with an altered balance between p-Ser194 FADD (increased) and total 
      FADD (decreased) in brain, which may favor its neuroplastic actions. The 
      interaction between p-FADD (upregulated) and neuronal pathways (downregulated) 
      could play a relevant role in mediating specific forms of structural and 
      behavioral neuroplasticity.
FAU - Ramos-Miguel, A
AU  - Ramos-Miguel A
AD  - Laboratorio de Neurofarmacologia, IUNICS, Universitat de les Illes Balears, and 
      Red Tematica de Investigacion Cooperativa en Salud (Trastornos Adictivos), Cra. 
      Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
FAU - Garcia-Fuster, M J
AU  - Garcia-Fuster MJ
FAU - Callado, L F
AU  - Callado LF
FAU - La Harpe, R
AU  - La Harpe R
FAU - Meana, J J
AU  - Meana JJ
FAU - Garcia-Sevilla, J A
AU  - Garcia-Sevilla JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090320
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (PEA15 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adult
MH  - Apoptosis Regulatory Proteins
MH  - Fas-Associated Death Domain Protein/*metabolism
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - *Neuronal Plasticity
MH  - Opioid-Related Disorders/*metabolism
MH  - Phosphoproteins/*physiology
MH  - Phosphorylation
MH  - Prefrontal Cortex/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Serine/metabolism
MH  - Signal Transduction
MH  - Time Factors
EDAT- 2009/03/24 09:00
MHDA- 2009/09/22 06:00
CRDT- 2009/03/24 09:00
PHST- 2008/11/27 00:00 [received]
PHST- 2009/02/27 00:00 [revised]
PHST- 2009/03/11 00:00 [accepted]
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/09/22 06:00 [medline]
AID - S0306-4522(09)00385-6 [pii]
AID - 10.1016/j.neuroscience.2009.03.028 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Jun 16;161(1):23-38. doi: 10.1016/j.neuroscience.2009.03.028. 
      Epub 2009 Mar 20.