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ER‐β mediates 17β‐estradiol attenuation of HIV‐1 Tat‐induced apoptotic signaling
Author(s) -
Adams Sheila M.,
Aksenova Marina V.,
Aksenov Michael Y.,
Mactutus Charles F.,
Booze Rosemarie M.
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20793
Subject(s) - estrogen receptor , estrogen , apoptosis , estrogen receptor beta , downregulation and upregulation , estrogen receptor alpha , neurodegeneration , microbiology and biotechnology , neuroprotection , signal transduction , caspase , chemistry , biology , programmed cell death , cancer research , pharmacology , medicine , endocrinology , biochemistry , disease , cancer , breast cancer , gene
The protective actions of estrogen have been well evaluated in various models of neurodegeneration. These neuroprotective mechanisms may include a direct neuronal antiapoptotic effect as estrogen modulates actions of key regulators of the mitochondrial/intrinsic apoptotic cascade. We tested the ability of estrogen to protect against apoptotic signaling in cortical cell cultures exposed to Tat 1‐86 (50 nM), and additionally, whether the beneficial actions of estrogen involved an estrogen receptor sensitive mechanism. We demonstrated that estrogen pretreatment significantly delayed Tat‐induced cell death in primary cortical cultures. Pretreatment with 17β‐estradiol (10 nM) attenuated the increased expression of antiapoptotic protein Bcl‐2, proapoptotic protein Bax and activation of caspases linked to mitochondrial apoptotic pathway following Tat exposure. In addition, select components of apoptotic pathway signaling appear more sensitive to estrogen receptor (ER) activation, as the addition of ER antagonist ICI 182780 reversed estrogen downregulation of Bax and caspase 3, while estrogen effects on Tat‐induced Bcl‐2 and caspase 9 expression were maintained. Moreover, the addition of preferential ERα and ERβ antagonists (MPP dihydrochloride and PHTPP) indicated that estrogen effects on caspase 3 may be mediated by both receptor subtypes, whereas, was more involved in estrogen effects on Bax. Our data suggest that estrogen intervenes against HIV‐1 Tat‐induced cortical neuronal dysfunction via intersecting mitochondrial apoptotic pathway signaling in an ER‐sensitive manner. Synapse 64:829–838, 2010. © 2010 Wiley‐Liss, Inc.