TY - JOUR
T1 - The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death
AU - Liu, Na
AU - Qiang, Wenan
AU - Kuang, Xianghong
AU - Thuillier, Philippe
AU - Lynn, William S.
AU - Wong, Paul K.Y.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/8
Y1 - 2002/8
N2 - Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and HIV neuroAIDS. In this study, we have investigated an agent, phenylbutyric acid, that ameliorates cell death in murine astrocytes infected with ts1 MoMuLV (ts1). Phenylbutyric acid, an aromatic short chain fatty acid, was shown to prevent the loss of catalase that occurs in ts1 infected astrocytes, and to prevent ts1-mediated cell death. Cell cotransfection studies demonstrated that phenylbutyric acid activates peroxisome proliferator receptors (PPARs) in astrocytes, and binds to the peroxisome proliferator-activated receptors α and γ. This observation suggests that the effects of PBA may be mediated by PPARs in astrocytes. Phenylbutyric acid also maintained catalase protein levels in brain of ts1-infected mice, and delayed the hindlimb paralysis caused by ts1 infection. Because PBA activates peroxisome proliferator-activated receptors and prevents loss of catalase, we suggest that ts1-induced oxidative stress in infected astrocytes that is alleviated by PBA is mediated via PPARα and/or PPARγ.
AB - Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and HIV neuroAIDS. In this study, we have investigated an agent, phenylbutyric acid, that ameliorates cell death in murine astrocytes infected with ts1 MoMuLV (ts1). Phenylbutyric acid, an aromatic short chain fatty acid, was shown to prevent the loss of catalase that occurs in ts1 infected astrocytes, and to prevent ts1-mediated cell death. Cell cotransfection studies demonstrated that phenylbutyric acid activates peroxisome proliferator receptors (PPARs) in astrocytes, and binds to the peroxisome proliferator-activated receptors α and γ. This observation suggests that the effects of PBA may be mediated by PPARs in astrocytes. Phenylbutyric acid also maintained catalase protein levels in brain of ts1-infected mice, and delayed the hindlimb paralysis caused by ts1 infection. Because PBA activates peroxisome proliferator-activated receptors and prevents loss of catalase, we suggest that ts1-induced oxidative stress in infected astrocytes that is alleviated by PBA is mediated via PPARα and/or PPARγ.
KW - Catalase
KW - Peroxisome proliferator-activated receptors
KW - Phenylbutyric acid
KW - Retrovirus-induced neurodegeneration
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U2 - 10.1080/13550280290100699
DO - 10.1080/13550280290100699
M3 - Article
C2 - 12161816
AN - SCOPUS:0036692295
VL - 8
SP - 318
EP - 325
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
SN - 1355-0284
IS - 4
ER -