已知糖皮质激素(GC)通过几种机制刺激胰腺β(β)细胞凋亡,包括氧化应激。我们先前的研究表明,通过减少谷胱甘肽S-转移酶P1(GSTP1),地塞米松诱导的胰腺β细胞凋亡增加,这是一种抗氧化酶。伊马替尼,这是一种酪氨酸激酶抑制剂,还发挥抗氧化作用。这项研究旨在验证我们的假设,即伊马替尼通过增加GSTP1表达和减少氧化应激来预防地塞米松诱导的胰腺β细胞凋亡。我们的结果表明,与对照组相比,地塞米松显着增加INS-1细胞的凋亡,伊马替尼显著降低地塞米松诱导的INS-1细胞凋亡。此外,与对照组相比,地塞米松显着增加了INS-1细胞中超氧化物的产生;然而,伊马替尼,当与地塞米松合用时,显著降低INS-1细胞中超氧化物的产生。地塞米松显著降低GSTP1、p-ERK1/2和BCL2蛋白表达,但显著增加了p-JNK,INS-1细胞中的p-p38和BAX蛋白表达均与对照相比。重要的是,伊马替尼显着改善地塞米松对GSTP1,p-ERK1/2,p-JNK表达的影响,p-p38MAPK,巴克斯,和BCL2。此外-6-(7-硝基-2,1,3-苯并恶二唑-4-基硫基)己醇(NBDHEX),这是一种GSTP1抑制剂,中和伊马替尼对地塞米松诱导的胰岛β细胞凋亡的保护作用。总之,伊马替尼通过增加GSTP1表达和降低氧化应激降低地塞米松诱导的胰岛β细胞凋亡。
Glucocorticoids (GCs) are known to stimulate pancreatic beta (β)-cell apoptosis via several mechanisms, including oxidative stress. Our previous study suggested an increase in dexamethasone-induced pancreatic β-cell apoptosis via a reduction of glutathione S-transferase P1 (GSTP1), which is an antioxidant enzyme. Imatinib, which is a tyrosine kinase inhibitor, also exerts antioxidant effect. This study aims to test our hypothesis that imatinib would prevent pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress. Our results revealed that dexamethasone significantly increased apoptosis in INS-1 cells when compared to the control, and that imatinib significantly decreased INS-1 cell apoptosis induced by dexamethasone. Moreover, dexamethasone significantly increased superoxide production in INS-1 cells when compared to the control; however, imatinib, when combined with dexamethasone, significantly reduced superoxide production in INS-1 cells. Dexamethasone significantly decreased GSTP1, p-ERK1/2, and BCL2 protein expression, but significantly increased p-JNK, p-p38, and BAX protein expression in INS-1 cells-all compared to control. Importantly, imatinib significantly ameliorated the effect of dexamethasone on the expression of GSTP1, p-ERK1/2, p-JNK, p-p38 MAPK, BAX, and BCL2. Furthermore-6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), which is a GSTP1 inhibitor, neutralized the protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone. In conclusion, imatinib decreases pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress.