Alterations in endothelial superoxide dismutase levels as a function of growth state in vitro.
Damage to the retinal vasculature in retinopathy of prematurity is primarily at the level of the growing neovascular front. This clinical observation in combination with experimental observations that correlate the induction of superoxide dismutase (SOD) activity with differentiation led to the hypothesis that the basis for the relative vulnerability to oxygen lies in the relative "undifferentiated" nature of proliferating endothelial cells (EC). To test this hypothesis, an in vitro model of microvascular EC was used and levels of SOD activity were assayed as a function of growth state and differentiation. The SOD activity was elevated significantly in EC that stopped growing as a contact-inhibited monolayer compared with its activity in cells in their log phase of growth. In addition, SOD levels were elevated in microvascular cells that stopped growing and were organized into a network of capillary-like tubes, the ultimate differentiated state of microvascular EC. To understand the mechanism of increases in SOD activity with differentiation, the effect of extracellular matrix synthesized by a confluent monolayer of EC was examined as was artificial growth arrest caused by mitomycin. Both treatments led to an increase in SOD activity over control cells. Thus, it is possible that SOD activity in cells is modulated by information provided from the extracellular matrix and "intracellular" signals that indicate cessation of cell growth. These data support the hypothesis that the growing front of retinal microvessels is more vulnerable to effects of oxygen-induced damage because of their relatively undifferentiated state with respect to the oxygen radical-scavenging enzyme system of SOD.
Smith
L E
LE
Department of Ophthalmology, Children's Hospital, Boston, Massachusetts.
Sweet
E
E
Freedman
S
S
D'Amore
P A
PA
D000302:Adrenal Cortex / Q000166:cytology / Q000201:enzymology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005109:Extracellular Matrix / Q000201:enzymology; D008937:Mitomycins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D008937:Mitomycins; D013482:Superoxide Dismutase