Estradiol prevents the focal cerebral ischemic injury-induced decrease of forkhead transcription factors phosphorylation.

Abstract

Estradiol prevents neuronal cell death through the inhibition of apoptotic signals. This study investigated whether estradiol modulates the anti-apoptotic signal through the activation of Akt and its downstream targets, including forkhead transcription factors FKHR and FHKRL1. Adult female rats were ovariectomied and treated with estradiol prior to middle cerebral artery occlusion (MCAO). Brains were collected 24 h after MCAO and infarct volumes were analyzed. Estradiol administration significantly reduced infarct volume and decreased the positive cells of TUNEL staining in the cerebral cortex. Potential activation was measured by phosphorylation of Akt at Ser473, pFKHR at Ser256, and pFKHRL1 at Thr32 using Western blot analysis and immunohistochemistry. Estradiol prevents the injury-induced decrease of pAkt, pFKHR, and pFKHRL1. Further, in the presence of estradiol, the interaction of pFKHRL1 and 14-3-3 increased, compared to that of oil-treated animals. Our findings suggest that estradiol plays a potent protective role against brain injury and that Akt activation and FKHR phosphorylation by estradiol mediated these protective effects.

• Authors: Chung Kil Won, Hyun Hwa Ji, Phil Ok Koh
• Journal: Neuroscience letters (Neurosci Lett) Vol. 398 Issue 1-2 Pg. 39-43 (May 01 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16423457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-3-3 Proteins
• FOXO3 protein, rat
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Nerve Tissue Proteins
• Foxo1 protein, rat
• Estradiol
• Proto-Oncogene Proteins c-akt

Topics

• 14-3-3 Proteins (metabolism)
• Animals
• Apoptosis
• Brain Ischemia (metabolism, pathology, prevention & control)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Estradiol (pharmacology)
• Female
• Forkhead Box Protein O3
• Forkhead Transcription Factors (metabolism)
• Immunohistochemistry
• Infarction, Middle Cerebral Artery (metabolism, pathology, prevention & control)
• Nerve Tissue Proteins (metabolism)
• Ovariectomy
• Phosphorylation
• Protein Binding
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley