PMID- 19054280
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 108
IP  - 1
DP  - 2009 Jan
TI  - Morphine and HIV-Tat increase microglial-free radical production and oxidative 
      stress: possible role in cytokine regulation.
PG  - 202-15
LID - 10.1111/j.1471-4159.2008.05756.x [doi]
AB  - Opiate abuse alters the progression of human immunodeficiency virus and may 
      increase the risk of neuroAIDS. As neuroAIDS is associated with altered 
      microglial reactivity, the combined effects of human immunodeficiency virus-Tat 
      and morphine were determined in cultured microglia. Specifically, experiments 
      determined the effects of Tat and morphine on microglial-free radical production 
      and oxidative stress, and on cytokine release. Data show that combined Tat and 
      morphine cause early and synergistic increases in reactive oxygen species, with 
      concomitant increases in protein oxidation. Furthermore, combined Tat and 
      morphine, but not Tat or morphine alone, cause reversible decreases in proteasome 
      activity. The effects of morphine on free radical production and oxidative stress 
      are prevented by pre-treatment with naloxone, illustrating the important role of 
      opioid receptor activation in these phenomena. While Tat is well known to induce 
      cytokine release from cultured microglia, morphine decreases Tat-induced release 
      of the cytokines tumor necrosis factor-alpha and interleukin-6, as well as the 
      chemokine monocyte chemoattractant protein-1 (MCP-1). Finally, experiments using 
      the reversible proteasome inhibitor MG115 show that temporary, non-cytotoxic 
      decreases in proteasome activity increase protein oxidation and decrease tumor 
      necrosis factor-alpha, interleukin-6, and MCP-1 release from microglia. Taken 
      together, these data suggest that oxidative stress and proteasome inhibition may 
      be involved in the immunomodulatory properties of opioid receptor activation in 
      microglia.
FAU - Turchan-Cholewo, Jadwiga
AU  - Turchan-Cholewo J
AD  - Department of Anatomy and Neurobiology, University of Kentucky, Lexington, 
      Kentucky, USA.
FAU - Dimayuga, Filomena O
AU  - Dimayuga FO
FAU - Gupta, Sunita
AU  - Gupta S
FAU - Keller, Jeffrey N
AU  - Keller JN
FAU - Knapp, Pamela E
AU  - Knapp PE
FAU - Hauser, Kurt F
AU  - Hauser KF
FAU - Bruce-Keller, Annadora J
AU  - Bruce-Keller AJ
LA  - eng
GR  - RR15592/RR/NCRR NIH HHS/United States
GR  - P01 DA019398-03/DA/NIDA NIH HHS/United States
GR  - R01 DA018633/DA/NIDA NIH HHS/United States
GR  - R01 NS046267-06/NS/NINDS NIH HHS/United States
GR  - P01 AG005119/AG/NIA NIH HHS/United States
GR  - P01 DA019398-04/DA/NIDA NIH HHS/United States
GR  - P01 AG005119-20A10012/AG/NIA NIH HHS/United States
GR  - P20 RR015592/RR/NCRR NIH HHS/United States
GR  - NS46267/NS/NINDS NIH HHS/United States
GR  - K02 DA027374/DA/NIDA NIH HHS/United States
GR  - DA19398/DA/NIDA NIH HHS/United States
GR  - P01 DA019398/DA/NIDA NIH HHS/United States
GR  - R01 NS046267/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081119
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cytokines)
RN  - 0 (HIV-TAT-survivin (T34A) protein)
RN  - 0 (Leupeptins)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Survivin)
RN  - 0 (carbobenzoxy-leucyl-leucyl-norvalinal)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 76I7G6D29C (Morphine)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Analgesics, Opioid/*pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis Regulatory Proteins/*pharmacology
MH  - Brain/cytology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Leupeptins/pharmacology
MH  - Mice
MH  - Microglia/*drug effects
MH  - Morphine/*pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Protease Inhibitors/pharmacology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - Survivin
MH  - tat Gene Products, Human Immunodeficiency Virus/*pharmacology
PMC - PMC2749479
MID - NIHMS133628
EDAT- 2008/12/05 09:00
MHDA- 2009/04/09 09:00
PMCR- 2010/01/01
CRDT- 2008/12/05 09:00
PHST- 2008/12/05 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/12/05 09:00 [entrez]
PHST- 2010/01/01 00:00 [pmc-release]
AID - JNC5756 [pii]
AID - 10.1111/j.1471-4159.2008.05756.x [doi]
PST - ppublish
SO  - J Neurochem. 2009 Jan;108(1):202-15. doi: 10.1111/j.1471-4159.2008.05756.x. Epub 
      2008 Nov 19.