Estrogen attenuates gp120- and tat1-72-induced oxidative stress and prevents loss of dopamine transporter function

David R. Wallace, Stephanie Dodson, Avindra Nath, Rosemarie M. Booze

Research output: Contribution to journalArticle

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Abstract

Postmenopausal women who are infected with HIV are at risk for experiencing dementia and Parkinson's-like symptoms associated with low levels of estrogen. Neurotoxic damage leading to these symptoms may involve HIV-associated proteins gp120 and/or tat1-72 (tat). Our hypothesis is that 17β-Estradiol (E2) is an effective agent for protection against gp120/tat-induced damage associated with increased oxidative stress, with particular focus on peroxynitrite-induced oxidative stress. We used SK-N-SH cells and striatal synaptosomes from Sprague-Dawley rats as model systems to assess neuroprotection by E2. Cells coincubated with SIN-1 (3-morpholinosydnonimine) or tat and gp120, together or separately, significantly increased oxidative stress on the SK-N-SH cells, as indicated by the increase in the levels of dichlorofluorescein (DCFH) fluorescence. These data suggest that a component of tat and gp120 neurotoxicity may be due to increased oxidative stress. Coincubation with E2 attenuated tat- and gp120-induced increase in fluorescence. Coincubation with progesterone had no effect on tat-induced fluorescence, whereas coincubation with the E2 antagonist ICI 182,780 and E2 completely prevented the effects observed with E2 alone. Both gp120 and tat decreased [3H] dopamine uptake into striatal synaptosomes by decreasing the Vmax of the dopamine transporter (DAT). Pretreatment of synaptosomes with E2 (100 nM) partially reversed this reduction. In conclusion, E2 appiears to be effective for preventing the oxidative stress and loss of DAT function associated with gp120/tat neurotoxicity.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalSynapse
Volume59
Issue number1
DOIs
Publication statusPublished - 1 Jan 2006

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Keywords

  • Dopamine transporter
  • Estrogen
  • HIV
  • Oxidative stress
  • Tat
  • gp120

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