Journal of Neuroimmune Pharmacology

, Volume 8, Issue 3, pp 691–704 | Cite as

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

  • Xiaosha Pang
  • Jun Panee
  • Xiangqian Liu
  • Marla J. Berry
  • Sulie L. Chang
  • Linda Chang


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.


HIV Methamphetamine Glutathione Lipid peroxidation Antioxidant Oxidative stress 



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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xiaosha Pang
    • 1
  • Jun Panee
    • 1
  • Xiangqian Liu
    • 2
    • 3
  • Marla J. Berry
    • 1
  • Sulie L. Chang
    • 2
  • Linda Chang
    • 4
  1. 1.Department of Cell and Molecular Biology, John A. Burns School of MedicineUniversity of Hawaii at ManoaHonoluluUSA
  2. 2.Institute of NeuroImmune Pharmacology and Department of Biological SciencesSeton Hall UniversitySouth OrangeUSA
  3. 3.Department of Histology and Embryology, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  4. 4.Department of MedicineJohn A. Burns School of Medicine, The Queen’s Medical CenterHonoluluUSA

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