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The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death

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Abstract

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.

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Authors and Affiliations

  1. M.D. Anderson Cancer Center, Science Park-Research Division, University of Texas, P.O. Box 389, 78957, Smithville, TX, USA

    Na Liu, Wenan Qiang, Xianghong Kuang, Philippe Thuillier, William S. Lynn & Paul K. Y. Wong

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  1. Na Liu
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  2. Wenan Qiang
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  3. Xianghong Kuang
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  4. Philippe Thuillier
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  5. William S. Lynn
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  6. Paul K. Y. Wong
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Corresponding author

Correspondence to Paul K. Y. Wong.

Additional information

This work was supported by NIH grants AI28283, MH57181, and NIEHS (Center Grant ES07784).

Equal contributions by these authors.

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Liu, N., Qiang, W., Kuang, X. et al. The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death. Journal of NeuroVirology 8, 318–325 (2002). https://doi.org/10.1080/13550280290100699

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  • DOI: https://doi.org/10.1080/13550280290100699

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