Estradiol prevents the injury-induced decrease of Akt activation and Bad phosphorylation.

Abstract

Estradiol prevents neuronal cell death through the inhibition of apoptotic signals and the activation of cell survival signals. This study investigated whether estradiol modulates the anti-apoptotic signal through the activation of Akt and its downstream targets, including Bad, Bcl-x(L), and 14-3-3. 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. We confirmed that estradiol significantly reduces infarct volume and decreases the positive cells of TUNEL staining in the cerebral cortex. Potential activation was measured by phosphorylation of Akt at Ser473 and Bad at Ser136 using Western blot analysis. Estradiol prevents the injury-induced decrease of pAkt, pBad, and Bcl-x(L). Further, in the presence of estradiol, the interaction of pBad and 14-3-3 increased, compared to that of oil-treated animals. Our findings suggest that estradiol prevents cell death due to brain injury and that Akt activation and Bad phosphorylation by estradiol mediated these protective effects.

• Authors: Chung Kil Won, Seung Jun Ha, Hae Sook Noh, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, Phil Ok Koh
• Journal: Neuroscience letters (Neurosci Lett) Vol. 387 Issue 2 Pg. 115-9 (Oct 21 2005) ISSN: 0304-3940 [Print] Ireland
• PMID: 16087293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-3-3 Proteins
• Bad protein, rat
• Bcl2l1 protein, rat
• Carrier Proteins
• Neuroprotective Agents
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• bcl-Associated Death Protein
• bcl-X Protein
• Estradiol
• Akt1 protein, rat
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• 14-3-3 Proteins (drug effects, metabolism)
• Animals
• Apoptosis (drug effects, physiology)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Carrier Proteins (drug effects, metabolism)
• Cerebral Infarction (drug therapy, physiopathology, prevention & control)
• Disease Models, Animal
• Down-Regulation (drug effects, physiology)
• Estradiol (pharmacology, therapeutic use)
• Female
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (drug effects, metabolism)
• Proto-Oncogene Proteins (drug effects, metabolism)
• Proto-Oncogene Proteins c-akt
• Proto-Oncogene Proteins c-bcl-2 (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects, physiology)
• bcl-Associated Death Protein
• bcl-X Protein