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Koziel 2017 IOC124

From Bioblast
The influence of chronic exposure to hypoxia on mitochondrial oxidative metabolism in human endothelial EA.hy926 cell.

Link: Mitochondr Physiol Network 22.07

Koziel A, Ogrodna K, Jarmuszkiewicz W (2017)

Event: IOC124

Endothelium is a monolayer of cells lining each blood vessel. Disturbances of endothelial functions are implicated in the development of many cardiovascular diseases. In endothelial cells, the ATP synthesis occurs in a major part via a glycolytic pathway. The slight dependence of endothelial cells on mitochondrial oxidative phosphorylation could suggest that mitochondria play no significant role in these cells. The general goal of our research is to study the aerobic metabolism of endothelial cells under physiological and pathophysiological conditions.

The goal of this study was to determine mitochondrial respiratory function in endothelial cells and isolated mitochondria and assess the influence of chronic hypoxia on the aerobic metabolism of these cells. Human umbilical vein endothelial cells (EA.hy926 cell line) were cultured for 6 days at 20% and 1% O2 concentrations.

In endothelial cells, chronic hypoxia provoked a shift from aerobic toward anaerobic catabolic metabolism. Growth of endothelial cells at 1% O2 tension did not change endothelial cells viability and mitochondrial biogenesis. However, elevated fermentation was observed. Under hypoxic conditions, mitochondrial respiration during carbohydrate, fatty acid and amino acid oxidation were declined, but ketogenic amino acid oxidation were increased. Hypoxia led to increased reactive oxygen species (ROS) generation (intracellular and mitochondrial), although antioxidant defence (superoxide dismutases SOD1 and SOD2, and uncoupling proteins, UCPs) were not escalated. Moreover, decreased UCP2 activity and expression were observed. Furthermore, in mitochondria from hypoxic cells, increased expression and activity of complex II, and decreased expression and activity of complex I were observed. The increased activity of complex II resulted in an elevation in succinate-sustained mitochondrial ROS generation, mainly through increased reverse electron transport. Chronic exposure to hypoxia lead to numerous changes in aerobic metabolism of endothelial cells. Endothelial mitochondria play a significant role in response to metabolic adaptation related to hypoxia. Our results point out an important role of succinate, complex II, and reverse electron transport in hypoxia adaptation of endothelial cells. Mitochondrial ROS could play a significant signalling role in endothelial cells under hypoxic conditions.


β€’ Bioblast editor: Beno M, Kandolf G


Labels: MiParea: Respiration, mt-Biogenesis;mt-density 

Stress:Hypoxia  Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Isolated mitochondria 


Pathway:



Support

This work was supported by the National Science Center Grants 2016/21/B/NZ3/00333 and 2012/07/N/NZ3/00495

Affiliations

Dept Bioenergetics, Fac Biology, Adam Mickiewicz Univ Poznan, Poland. - [email protected]