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Regional Variations of Antioxidant Capacity and Oxidative Stress Responses in HIV-1 Transgenic Rats With and Without Methamphetamine Administration

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Abstract

HIV infection and methamphetamine (Meth) abuse both may lead to oxidative stress. This study used HIV-1 transgenic (HIV-1Tg) rats to investigate the independent and combined effects of HIV viral protein expression and low dose repeated Meth exposure on the glutathione (GSH)-centered antioxidant system and oxidative stress in the brain. Total GSH content, gene expression and/or enzymatic activities of glutamylcysteine synthetase (GCS), gamma-glutamyltransferase (GGT), glutathione reductase (GR), glutathione peroxidase (GPx), glutaredoxin (Glrx), and glutathione-s-transferase (GST) were measured. The protein expression of cystine transporter (xCT) and oxidative stress marker 4-hydroxynonenal (HNE) were also analyzed. Brain regions studied include thalamus, frontal and remainder cortex, striatum, cerebellum and hippocampus. HIV-1Tg rats and Meth exposure showed highly regional specific responses. In the F344 rats, the thalamus had the highest baseline GSH concentration and potentially higher GSH recycle rate. HIV-1Tg rats showed strong transcriptional responses to GSH depletion in the thalamus. Both HIV-1Tg and Meth resulted in decreased GR activity in thalamus, and decreased Glrx activity in frontal cortex. However, the increased GR and Glrx activities synergized with increased GSH concentration, which might have partially prevented Meth-induced oxidative stress in striatum. Interactive effects between Meth and HIV-1Tg were observed in thalamus on the activities of GCS and GGT, and in thalamus and frontal cortex on Glrx activity and xCT protein expression. Findings suggest that HIV viral protein and low dose repeated Meth exposure have separate and combined effects on the brain’s antioxidant capacity and the oxidative stress response that are regional specific.

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Acknowledgments

This study was made possible by grants from the National Institutes of Health (NIH): U54NS56883, 5P20RR016467-11 and 8P20GMl03466-11 (INBRE II), 5G12RR003061 and 8G12MD007601 (RCMI/BRIDGES), 2K24DA016170 (to LC) and 2 K02016149 (to SLC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street BSB 222, Honolulu, HI, 96813, USA

    Xiaosha Pang, Jun Panee & Marla J. Berry

  2. Institute of NeuroImmune Pharmacology and Department of Biological Sciences, Seton Hall University, South Orange, NJ, 07079, USA

    Xiangqian Liu & Sulie L. Chang

  3. Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Xiangqian Liu

  4. Department of Medicine, John A. Burns School of Medicine, The Queen’s Medical Center, 1356 Lusitana Street, 7th floor, Honolulu, HI, 96813, USA

    Linda Chang

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  1. Xiaosha Pang
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  2. Jun Panee
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  6. Linda Chang
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Correspondence to Linda Chang.

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Xiaosha Pang and Jun Panee contributed equally to this work.

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Pang, X., Panee, J., Liu, X. et al. Regional Variations of Antioxidant Capacity and Oxidative Stress Responses in HIV-1 Transgenic Rats With and Without Methamphetamine Administration. J Neuroimmune Pharmacol 8, 691–704 (2013). https://doi.org/10.1007/s11481-013-9454-8

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