Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow region, Russia.
Scientific and Educational Center in Chernogolovka of Moscow Region State University, Mytishchi, Moscow region, Russia.
Bull Exp Biol Med. 2020 May;169(1):169-175. doi: 10.1007/s10517-020-04844-3. Epub 2020 Jun 5.
The effect of inhibition of the tumor suppressor p53 on the antioxidant system genes expression under the influence of cytotoxic compounds of the platinum group was studied. It was found that the action of platinum(II) and platinum(IV) complexes induced accumulation of p53 protein with a maximum in 12 h, which was confirmed by an increase in the expression of the P21 gene, the target gene of the p53 protein. It was shown that the action of platinum complexes activated the expression of catalase and superoxide dismutase 2 genes. Suppression of p53 protein functions with specific inhibitor α-piphitrin under the action of platinum complexes reduced the expression of catalase and superoxide dismutase 2 genes and the target gene P21, which attested to the p53-dependent regulation of these genes.
研究了肿瘤抑制因子 p53 的抑制作用对细胞毒性铂族化合物影响下抗氧化系统基因表达的影响。结果发现,铂(II)和铂(IV)配合物的作用诱导 p53 蛋白的积累,在 12 小时达到最大值,这通过 p53 蛋白的靶基因 P21 基因的表达增加得到证实。结果表明,铂配合物的作用激活了过氧化氢酶和超氧化物歧化酶 2 基因的表达。在铂配合物的作用下,用特异性抑制剂α-皮啡亭抑制 p53 蛋白的功能,降低了过氧化氢酶和超氧化物歧化酶 2 基因及其靶基因 P21 的表达,这证明了这些基因的 p53 依赖性调节。