1. Hypoxia activates autophagy by Akt/FoxO1 pathway in fish cells.
- Author
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Kang Chen, Linlin Shi, Hong Liu, and Huanling Wang
- Subjects
HYPOXEMIA ,AUTOPHAGY ,OXIDATIVE stress ,REACTIVE oxygen species ,TRANSMISSION electron microscopy - Abstract
Hypoxia, a common environmental condition, can affect cell survival and physiological function by triggering oxidative stress. Akt/FoxO pathway has been proven to play a non-negligible role in the regulation of autophagy. However, the role of Akt/FoxO pathway in hypoxia-induced autophagy is unclear in fish. Therefore, in this study, grass carp hepatocyte cells (L8824) were treated by CoCl
2 to simulate hypoxia, and the results showed that CoCl2 can increase the expression of Hif-1a protein at different concentrations or different treatment time. Further study found that hypoxia increased intracellular reactive oxygen species (ROS) level, and the expression of autophagy-related genes (LC3-II, pink1, beclin-1 and p62) and foxO1a/1b. The mitochondrial membrane potential (ΔΨm) was also depolarized, and autophagosomes were intriguingly detected by transmission electron microscope (TEM) after the treatment of hypoxia. Moreover, hypoxia inhibited Akt phosphorylation, while PI3K/Akt pathway inhibitor, LY294002 significantly up-regulated the expression of foxO1a/1b and autophagy-related genes. Additionally, silencing foxo1b also resulted in down-regulation of autophagy-related genes. It was demonstrated that hypoxia induced autophagy via Akt/FoxO1 pathway. These results will provide a new light on further understanding the role of Akt/FoxO pathway in the response to hypoxia in fish. [ABSTRACT FROM AUTHOR]- Published
- 2024
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