MOLECULAR INSIGHTS INTO CELLULAR ADAPTATION TO HYPOXIC MICROENVIRONMENTS

Abstract

Hypoxia, which means the lack of oxygen, is a severe microenvironmental variable, which has a tremendous impact on cellular behavior and survival. It contributes immensely to physiological adaptation and pathological course, especially in cancer, ischemic disorders, and metabolic diseases. This paper explores the cellular adaptive pathways to hypoxic microenvironment, and its associated critical signaling pathways, such as hypoxia-inducible factor-1 alpha (HIF-1 -), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and apoptotic signaling through p53. The models of in vitro cell culture were subjected to controlled hypoxic conditions and the gene and protein expression were assessed by RT-qPCR and Western blot. The findings reveal that early hypoxia causes a remarkable increase in HIF-1 and adaptive genes, and temporary activation of survival factors like PI3K/ Akt. Nevertheless, with a long period of hypoxia, there is mitochondrial dysfunction, oxidative stress, and the activation of pro-apoptotic proteins such as p53, BAX, and caspase-3. These results indicate that there is a dynamic shift between adaptive mechanism to programmed cell death in the case of prolonged hypoxia. Altogether, this research presents a combined insight into the hypoxia-regulated signal networks and highlights their promise of being used as a treatment option in diseases related to hypoxia.