Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-acetate- or hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial cells

Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-acetate- or hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial cells
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DOI:
10.1016/s0304-3835(01)00821-7
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发表时间:
2002-04-08
期刊:
影响因子:
9.7
通讯作者:
Lee, YS
Lee, YS
中科院分区:
医学1区
文献类型:
--
作者:
Kang, KS;Yun, JW;Lee, YS

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细胞凋亡过程与癌症和神经退行性疾病如阿尔茨海默病、帕金森病等有关。骨骼肌中大量存在的β-丙氨酰-L-组氨酸(L-肌肽)被认为具有抗氧化活性。我们研究了 L-肌肽是否可以预防 12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 或过氧化氢 (H2O2) 诱导的涉及 v-myc 转化大鼠肝上皮细胞(WB-myc 细胞)线粒体的细胞凋亡。 L-肌肽可防止 TPA 和 H2O2 诱导的 DNA 断裂、线粒体膜电位的丧失,并阻止细胞色素 c 释放到细胞质中。随后,L-肌肽处理的细胞中聚(ADP-核糖)聚合酶的裂解显着减少。然而,蛋白质印迹分析显示,TPA 和 H2O2 处理后 12 小时内 p53 蛋白水平没有变化。因此,这些结果表明,L-肌肽(一种抗氧化剂)可以通过线粒体途径保护 H2O2 和 TPA 诱导的细胞凋亡。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Apoptotic Processes have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease etc. beta-Alanyl-L-histidine (L-carnosine), occurring abundantly in skeletal muscles has been suggested to possess antioxidative activity. We investigated whether L-carnosine prevents 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hydrogen peroxide (H2O2)-induced apoptosis involving mitochondria in the v-myc transformed rat liver epithelial cells (WB-myc cells). L-Carnosine prevented both TPA- and H2O2-induced DNA fragmentation, the loss of mitochondrial membrane potentials and blocked the release of cytochrome c into cytosol. Subsequently, the cleavages of poly (ADP-ribose) polymerase were significantly reduced in L-carnosine-treated cells. However, western blotting analysis revealed that p53 protein level did not change for 12 h after TPA- and H2O2-treatment. Therefore, these results suggested that L-carnosine, an antioxidant, protected both H2O2- and TPA-induced apoptosis through mitochondrial pathways. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.