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The interplay of ROS and the PI3K/Akt pathway in autophagy regulation
Biotechnology and Applied Biochemistry ( IF 2.8 ) Pub Date : 2021-01-14 , DOI: 10.1002/bab.2104
Lakhan Kma 1 , Taranga Jyoti Baruah 2
Affiliation  

Autophagy causes the breakdown of damaged proteins and organelles to their constituent components. The phosphatidylinositol 3-kinase (PI3K) pathway played an important role in regulating the autophagic response of cells in response to changing reactive oxygen species (ROS) levels. The PI3K α catalytic subunit inhibits autophagy, while its β catalytic subunit promotes autophagy in response to changes in ROS levels. The downstream Akt protein acts against autophagy initiation in response to increases in ROS levels under nutrient-rich conditions. Akt acts by activating a mechanistic target of the rapamycin complex 1 (mTORC1) and by arresting autophagic gene expression. The AMP-activated protein kinase (AMPK) protein counteracts the Akt actions. mTORC1 and mTORC2 inhibit autophagy under moderate ROS levels, but under high ROS levels, mTORC2 can promote cellular senescence via autophagy. Phosphatase and tensin homolog (PTEN) protein are the negative regulators of the PI3K pathway, and it has proautophagic activities. Studies conducted on cells treated with flavonoids and ionizing radiation showed that the moderate increase in ROS levels in the flavonoid-treated groups corresponded with higher PTEN levels and lowered Akt levels leading to a higher occurrence of autophagy. In contrast, higher ROS levels evoked by ionizing radiation caused a lowering of the incidence of autophagy.

中文翻译:

ROS与PI3K/Akt通路在自噬调控中的相互作用

自噬导致受损蛋白质和细胞器分解为其组成成分。磷脂酰肌醇 3-激酶 (PI3K) 通路在调节细胞响应活性氧 (ROS) 水平变化的自噬反应中发挥重要作用。PI3K α 催化亚基抑制自噬,而其 β 催化亚基促进自噬以响应 ROS 水平的变化。下游 Akt 蛋白在营养丰富的条件下响应于 ROS 水平的增加而对抗自噬启动。Akt 通过激活雷帕霉素复合物 1 (mTORC1) 的机械靶标和阻止自噬基因表达发挥作用。AMP 活化蛋白激酶 (AMPK) 蛋白抵消 Akt 作用。mTORC1 和 mTORC2 在中等 ROS 水平下抑制自噬,但在高 ROS 水平下,mTORC2可以通过自噬促进细胞衰老。磷酸酶和张力蛋白同源物 (PTEN) 蛋白是 PI3K 通路的负调节因子,具有促自噬活性。对用类黄酮和电离辐射处理的细胞进行的研究表明,类黄酮处理组中 ROS 水平的适度增加与更高的 PTEN 水平相对应,而降低的 Akt 水平则导致更高的自噬发生率。相比之下,电离辐射引起的较高 ROS 水平导致自噬发生率降低。对用类黄酮和电离辐射处理的细胞进行的研究表明,类黄酮处理组中 ROS 水平的适度增加与更高的 PTEN 水平相对应,而降低的 Akt 水平则导致更高的自噬发生率。相比之下,电离辐射引起的较高 ROS 水平导致自噬发生率降低。对用类黄酮和电离辐射处理的细胞进行的研究表明,类黄酮处理组中 ROS 水平的适度增加与更高的 PTEN 水平相对应,而降低的 Akt 水平则导致更高的自噬发生率。相比之下,电离辐射引起的较高 ROS 水平导致自噬发生率降低。
更新日期:2021-01-14
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