title: Endothelial cells maintain a reduced redox environment even as mitochondrial function declines.
abstract: Human umbilical vein endothelial cells (HUVECs) are an endothelial model of replicative senescence. Oxidative stress, possibly due to dysfunctional mitochondria, is believed to play a key role in replicative senescence and atherosclerosis, an age-related vascular disease. In this study, we determined the effect of cell division on genomic instability, mitochondrial function, and redox status in HUVECs that were able to replicate for approximately 60 cumulative population doublings (CPD). After 20 CPD, the nuclear genome deteriorated and the protein content of the cell population increased. This indicated an increase in cell size, which was accompanied by an increase in oxygen consumption, ATP production, and mitochondrial genome copy number and approximately 10% increase in mitochondrial mass. The antioxidant capacity increased, as seen by an increase in reduced glutathione, glutathione peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase. However, by CPD 52, the latter two enzymes decreased, as well as the ratio of mitochondrial-to-nuclear genome copies, the mitochondrial mass, and the oxygen consumption per milligram of protein. Our results signify that HUVECs maintain a highly reducing (GSH) environment as they replicate despite genomic instability and loss of mitochondrial function.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana Health Sciences Center, Shreveport, Louisiana 71130, USA.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Carlisle
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Rhoads
authors.forename: Tak Yee
authors.initials: TY
authors.lastname: Aw
authors.forename: Lynn
authors.initials: L
authors.lastname: Harrison
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism; D016678:Genome; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004798:Enzymes; D011506:Proteins; D017382:Reactive Oxygen Species; D005978:Glutathione; D019803:Glutathione Disulfide