PMID- 25586717
OWN - NLM
STAT- MEDLINE
DCOM- 20151112
LR  - 20240322
IS  - 1557-1904 (Electronic)
IS  - 1557-1890 (Print)
IS  - 1557-1890 (Linking)
VI  - 10
IP  - 1
DP  - 2015 Mar
TI  - Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-gamma 
      via a TNF-alpha/JNK- mediated mechanism.
PG  - 55-73
LID - 10.1007/s11481-014-9573-x [doi]
AB  - Cocaine abuse represents an immense societal health and economic burden for which 
      no effective treatment currently exists. Among the numerous intracellular 
      signaling cascades impacted by exposure to cocaine, increased and aberrant 
      production of pro-inflammatory cytokines in the CNS has been observed. 
      Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma 
      (RXR-gamma) in brains of mice chronically exposed to cocaine. Through obligate 
      heterodimerization with a number of nuclear receptors, RXRs serve as master 
      regulatory transcription factors, which can potentiate or suppress expression of 
      a wide spectrum of genes. Little is known about the regulation of RXR levels, but 
      previous studies indicate cellular stressors such as cytokines negatively 
      regulate levels of RXRs in vitro. To evaluate the mechanism underlying the 
      cocaine-induced decreases in RXR-gamma levels observed in vivo, we exposed neurons to 
      cocaine in vitro and examined pathways which may contribute to disruption in RXR 
      signaling, including activation of stress pathways by cytokine induction. In 
      these studies, we provide the first evidence that cocaine exposure disrupts 
      neuronal RXR-gamma signaling in vitro by promoting its nuclear export and 
      degradation. Furthermore, we demonstrate this effect may be mediated, at least in 
      part, by cocaine-induced production of TNF-alpha and its downstream effector 
      c-Jun-NH-terminal kinase (JNK). Findings from this study are therefore applicable 
      to both cocaine abuse and to pathological conditions characterized by 
      neuroinflammatory factors, such as neurodegenerative disease.
FAU - Kovalevich, Jane
AU  - Kovalevich J
AD  - Department of Neuroscience, Temple University School of Medicine, Medical 
      Education Research Building, 3500 North Broad Street, Philadelphia, PA, 19140, 
      USA.
FAU - Yen, William
AU  - Yen W
FAU - Ozdemir, Ahmet
AU  - Ozdemir A
FAU - Langford, Dianne
AU  - Langford D
LA  - eng
GR  - P30 MH092177/MH/NIMH NIH HHS/United States
GR  - R21 DA029523/DA/NIDA NIH HHS/United States
GR  - DA029523/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150114
PL  - United States
TA  - J Neuroimmune Pharmacol
JT  - Journal of neuroimmune pharmacology : the official journal of the Society on 
      NeuroImmune Pharmacology
JID - 101256586
RN  - 0 (Cytokines)
RN  - 0 (GAP-43 Protein)
RN  - 0 (Retinoid X Receptor gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Nucleus/*metabolism
MH  - Cocaine/*pharmacology
MH  - Cytokines/metabolism
MH  - GAP-43 Protein/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Immunohistochemistry
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/drug effects/*metabolism
MH  - Plasmids/genetics
MH  - Retinoid X Receptor gamma/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC4336643
MID - NIHMS655666
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2015/01/15 06:00
MHDA- 2015/11/13 06:00
PMCR- 2016/03/01
CRDT- 2015/01/15 06:00
PHST- 2014/05/27 00:00 [received]
PHST- 2014/11/26 00:00 [accepted]
PHST- 2015/01/15 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2015/11/13 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 10.1007/s11481-014-9573-x [doi]
PST - ppublish
SO  - J Neuroimmune Pharmacol. 2015 Mar;10(1):55-73. doi: 10.1007/s11481-014-9573-x. 
      Epub 2015 Jan 14.