Abstract | UNLABELLED:
Estrogen is associated with increased heat shock protein (HSP)72 and protection during hypoxia-reoxygenation in cardiomyocytes from adult male rats, as previously reported. We have also reported that female rats have more cardiac HSP72 than males. We hypothesized that, despite higher endogenous estrogen levels and higher baseline HSP72, 17 beta-estradiol treatment would still result in increased HSP72 and protection during hypoxia-reoxygenation in cardiomyocytes from females. METHODS/RESULTS: Cardiac cells isolated from adult female rats were treated for 12 hr with 17 beta-estradiol (0.1, 10, or 50 microM), tamoxifen, (10 or 25 microM; estrogen receptor agonist/antagonist), geldanamycin (2, 5, or 10 microg/ml; inactivates HSP90, preventing interaction with HSF1), or vehicle. Western blot analyses revealed that treatment with 17 beta-estradiol (10 or 50 microM), tamoxifen (25 microM), and geldanamycin (all doses) resulted in significant increases in HSP72. Electromobility shift assays revealed activation of HSF1 by 2 to 3 hr, and NF kappa B activation by 15 min. HSP72 induction via HSF1 activation was confirmed using transcription factor decoys containing the heat shock element, which prevented the estrogen-related HSP72 induction. Estrogen pretreatment resulted in decreased LDH release during 24 hr hypoxia. This protective effect persisted despite decoy-mediated blockade of nuclear HSF1 binding. However, transfection with an NF?B decoy not only prevented an estrogen-associated increase in HSP72, but also abolished the estrogen-related protection during hypoxia. CONCLUSIONS:
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Authors | Karyn L Hamilton, S Gupta, A A Knowlton |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 36
Issue 4
Pg. 577-84
(Apr 2004)
ISSN: 0022-2828 [Print] England |
PMID | 15081317
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Benzoquinones
- Estrogens
- HSP72 Heat-Shock Proteins
- HSP90 Heat-Shock Proteins
- Heat-Shock Proteins
- Lactams, Macrocyclic
- NF-kappa B
- Quinones
- Tamoxifen
- Estradiol
- L-Lactate Dehydrogenase
- Oxygen
- geldanamycin
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Topics |
- Animals
- Benzoquinones
- Blotting, Western
- Cells, Cultured
- Dose-Response Relationship, Drug
- Estradiol
(metabolism)
- Estrogens
(metabolism)
- Female
- HSP72 Heat-Shock Proteins
- HSP90 Heat-Shock Proteins
(metabolism)
- Heat-Shock Proteins
(metabolism)
- Hypoxia
- L-Lactate Dehydrogenase
(metabolism)
- Lactams, Macrocyclic
- Myocytes, Cardiac
(metabolism)
- NF-kappa B
(metabolism)
- Oxygen
(metabolism)
- Quinones
(pharmacology)
- Rats
- Signal Transduction
- Tamoxifen
(pharmacology)
- Transcription, Genetic
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