Role of effectors on hypoxia due to nitric oxide production in human alveolar epithelial cells and oxygen depletion in human hepatocytes

The effect of hypoxia on cell viability, proliferation and possible induced apoptosis in human alveolar epithelial cells and human hepatocytes is not clearly understood.In cultured human alveolar epithelial cells, IL-1β, TNF-α and INF-γ stimulated the nitric oxide production and resulted with inflammation manifested by hypoxia and apoptosis.In cultured hepatocytes,enhanced expression of superoxide dismutase and glutathione reductase enzymes indicated hypoxia associated with the enhanced level of cAMP dependent phosphodiesterase, NADPH dependentCytochrome C Oxidase enzyme activities due to energy insufficiency in hepatocyte cultured medium.Both hypoxia and energy insufficiency reduced hepatocyte viability.We propose that extent of inflammation leading to hypoxia initially and programmed cell death later both can enhance the MRI visible edema fluid content in lungs due to oxygen and energy insufficiency to surviving inflammatory alveolar epithelial cells.The mechanism of A549 cell damage due to nitric oxide (NO) production included: Cytokines regulated the expression of nitric oxide synthase (NOS) through NF-κB activation; Cofactor tetrahydro biopterin-catalyzed synthesis of iducible nitric oxide synthase (iNOS) enzyme.The NO production and increased level of NOS expression lead to Na⁺ ion transport and cell proliferation with differentiation or apoptosis.Hypoxic human alveolar epithelial cells showed the possibility of NO production associated with the decrease of their viability and rapid increase of apoptosis. In conclusion, increased level of NO production can be a cause of hypoxia induced apoptosis and possibly MRI visible indicator of inflamed alveolar cell viability. High resolution MRI can track these sites of inflammation in lungs.