Soy Isoflavones Genistein and Daidzein Exert Anti-Apoptotic Actions via a Selective ER-mediated Mechanism in Neurons following HIV-1 Tat(1-86) Exposure

作者：Adams Sheila M^*; Aksenova Marina V; Aksenov Michael Y; Mactutus Charles F; Booze Rosemarie M

来源：PLos One, 2012, 7(5): e37540.

DOI：10.1371/journal.pone.0037540

Background: HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity. %26lt;br%26gt;Methodology/Principal Findings: We demonstrate in primary cortical cell cultures that 17 beta-estradiol or isoflavones (genistein or daidzein) attenuate Tat(1-86)-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ER alpha or ER beta specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ER beta selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling. %26lt;br%26gt;Conclusions/Significance: Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons.

• 出版日期2012-5-22