Proliferation dynamics in cultured skin fibroblasts from Down syndrome subjects.
With a view to better understanding the role of oxidant/antioxidant variables in proliferation dynamics of somatic cells, we explored the relationships among superoxide dismutase (SOD) activity, glutathione peroxidase (Gpx) activity, reactive oxygen intermediates (ROI), and indices of cellular proliferation and senescence in cultured fibroblasts from Down syndrome and normal donors. We found that Down syndrome cells had a significantly slower proliferative rate, but attain replicative senescence at similar population doubling (PD) as control cells. Irrespective of donor origin, the number of PD until replicative senescence was positively correlated with Gpx activity (r = 0.784, P = 0.007). In addition, the presence of exogenous catalase in the growth medium significantly extended the number of PD until replicative senescence (P = 0.011). The loss of telomere repeats per PD was not different between Down syndrome cells and controls. However, SOD activity was inversely correlated with the loss of telomere repeats per PD. Collectively, these findings suggest that replicative senescence ultimately relates to mechanisms downstream to SOD (i.e., Gpx and catalase) and confirmed previous observations about inverse relationships between SOD activity and telomere repeat loss per cellular replication.
Hypertension Research Center, MSB, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark NJ 07103, USA.
Masayuki
M
Kimura
Xiaojian
X
Cao
Joan
J
Skurnick
Michael
M
Cody
Patricia
P
Soteropoulos
Abraham
A
Aviv
D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004314:Down Syndrome / Q000503:physiopathology*; D005347:Fibroblasts / Q000166:cytology*; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D013482:Superoxide Dismutase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase