Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, Republic of Korea.
Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, Republic of Korea.
Brain Res Bull. 2017 Sep;134:63-71. doi: 10.1016/j.brainresbull.2017.07.008. Epub 2017 Jul 11.
The taxifolin effect on the cholesterol oxidation product-induced neuronal apoptosis was investigated using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells. 7-ketocholesterol induced phosphorylation of Akt, and increase in the levels of cytosolic and nuclear NF-κB p65, cytosolic NF-κB p50 and cytosolic phosphorylated-IκB-α in PC12 cells. The cholesterol oxidation products also induced a decrease in the levels of Bid and Bcl-2, increase in the levels of p53 and Bax, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases (-8, -9 and -3), production of reactive oxygen species, depletion of GSH and cell death in both cell lines. Taxifolin, N-acetylcysteine, trolox, Akt inhibitor and Bay11-7085 attenuated the cholesterol oxidation product-induced changes in the apoptosis-related protein levels, activation of the Akt and NF-κB, reactive oxygen species production, GSH depletion and cell death. These results show that taxifolin may reduce the cholesterol oxidation product-induced neuronal apoptosis by suppressing the Akt and NF-κB activation-mediated cell death. The suppressive effect appears to be attributed to the inhibition of reactive oxygen species production and GSH depletion.
用分化的 PC12 细胞和人神经母细胞瘤 SH-SY5Y 细胞研究了圣草酚对胆固醇氧化产物诱导的神经元凋亡的影响。7-酮胆固醇诱导 Akt 的磷酸化，以及 PC12 细胞中细胞质和核 NF-κB p65、细胞质 NF-κB p50 和细胞质磷酸化-IκB-α水平的增加。胆固醇氧化产物还诱导 Bid 和 Bcl-2 水平降低，p53 和 Bax 水平升高，线粒体跨膜电位丧失，细胞色素 c 释放，半胱天冬酶（-8、-9 和 -3）激活，活性氧产生，GSH 耗竭和两种细胞系中的细胞死亡。圣草酚、N-乙酰半胱氨酸、Trolox、Akt 抑制剂和 Bay11-7085 减弱了胆固醇氧化产物诱导的凋亡相关蛋白水平、Akt 和 NF-κB 激活、活性氧产生、GSH 耗竭和细胞死亡的变化。这些结果表明，圣草酚可能通过抑制 Akt 和 NF-κB 激活介导的细胞死亡来减少胆固醇氧化产物诱导的神经元凋亡。抑制作用似乎归因于抑制活性氧产生和 GSH 耗竭。
