Soy isoflavones genistein and daidzein exert anti-apoptotic actions via a selective ER-mediated mechanism in neurons following HIV-1 Tat(1-86) exposure.
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.


RESULTS
We demonstrate in primary cortical cell cultures that 17β-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 ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling.


CONCLUSIONS
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.
Department of Psychology, University of South Carolina, Columbia, South Carolina, United States of America. Adamssm4@mailbox.sc.edu
Sheila M
SM
Adams
Marina V
MV
Aksenova
Michael Y
MY
Aksenov
Charles F
CF
Mactutus
Rosemarie M
RM
Booze
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D015497:HIV-1; D007529:Isoflavones / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D010446:Peptide Fragments / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D010446:Peptide Fragments; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D054322:tat Gene Products, Human Immunodeficiency Virus; C004742:daidzein; D019833:Genistein