Won Chung Kil, Ha Seung Jun, Noh Hae Sook, Kang Sang Soo, Cho Gyeong Jae, Choi Wan Sung, Koh Phil Ok
Department of Anatomy, College of Veterinary Medicine and Institute of Animal Science, Gyeongsang National University, Chinju 660-701, South Korea.
Neurosci Lett. 2005 Oct 21;387(2):115-9. doi: 10.1016/j.neulet.2005.07.021.
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.
雌二醇通过抑制凋亡信号和激活细胞存活信号来防止神经元细胞死亡。本研究调查了雌二醇是否通过激活Akt及其下游靶点（包括Bad、Bcl-x(L)和14-3-3）来调节抗凋亡信号。成年雌性大鼠接受卵巢切除术，并在大脑中动脉闭塞（MCAO）之前用雌二醇进行治疗。MCAO后24小时收集大脑并分析梗死体积。我们证实，雌二醇显著减小梗死体积，并减少大脑皮质中TUNEL染色的阳性细胞。使用蛋白质印迹分析通过Ser473位点的Akt磷酸化和Ser136位点的Bad磷酸化来测量潜在的激活情况。雌二醇可防止损伤诱导的pAkt、pBad和Bcl-x(L)减少。此外，与用油处理的动物相比，在存在雌二醇的情况下，pBad与14-3-3的相互作用增加。我们的研究结果表明，雌二醇可防止因脑损伤导致的细胞死亡，并且雌二醇介导的Akt激活和Bad磷酸化发挥了这些保护作用。
