Yeste-Velasco Marc, Folch Jaume, Jiménez Andres, Rimbau Victor, Pallàs Mercè, Camins Antoni
Unitat de Farmacologia i Farmacognòsia and Institut de Biomedicina (IBUB), Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain.
Eur J Pharmacol. 2008 Jul 7;588(2-3):239-43. doi: 10.1016/j.ejphar.2008.04.019. Epub 2008 Apr 11.
The antioxidant effects of lithium and SB-415286, two glycogen synthase kinase-3 beta (GSK-3 beta) inhibitors, were studied in cerebellar granule neurons by measuring changes in 2, 7-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescence. GSK-3 beta inhibitors inhibit apoptosis mediated by serum and potassium withdrawal (S/K withdrawal) and GSK-3 beta activation, as measured by beta-catenin degradation. Furthermore, as both drugs prevent mitochondrial apoptosis inducing factor (AIF) release, these data indicate that GSK-3 beta inhibitors prevent caspase-independent apoptosis in cerebellar granule neurons induced by S/K withdrawal. While the most specific GSK-3 beta inhibitor, SB-415286, demonstrated antioxidant effects, Li+ 10 mM did not. These results indicate that lithium 10 mM and SB-415286 20 microM exert anti-apoptotic effects in cases of S/K withdrawal mediated by GSK-3 beta inhibition. However, these antioxidant properties are independent of GSK-3 beta inhibition and prevention of mitochondrial AIF release.
通过测量二氯二氢荧光素二乙酸酯（H2DCFDA）荧光变化，研究了两种糖原合酶激酶-3β（GSK-3β）抑制剂锂和SB-415286在小脑颗粒神经元中的抗氧化作用。GSK-3β抑制剂可抑制血清和钾离子撤除（S/K撤除）介导的细胞凋亡以及GSK-3β激活，这可通过β-连环蛋白降解来衡量。此外，由于这两种药物均可阻止线粒体凋亡诱导因子（AIF）释放，这些数据表明GSK-3β抑制剂可预防S/K撤除诱导的小脑颗粒神经元中的非半胱天冬酶依赖性细胞凋亡。虽然最具特异性的GSK-3β抑制剂SB-415286具有抗氧化作用，但10 mM的Li+却没有。这些结果表明，10 mM锂和20 μM SB-415286在GSK-3β抑制介导的S/K撤除情况下发挥抗凋亡作用。然而，这些抗氧化特性与GSK-3β抑制和线粒体AIF释放的预防无关。
