Effects of oxygen, growth state, and senescence on the antioxidant responses of WI-38 fibroblasts.
Mitotically active, growth-arrested cells and proliferatively senescent cultures of human fetal lung fibroblasts (WI-38) were exposed to six different oxygen tensions for various lengths of time and then analyzed to determine the responses of their antioxidant defense system. Glutathione (GSH) concentration increased as a function of ambient oxygen tension in early passage cultures; the effect was larger in exponentially growing cultures than in those in a state of contact-inhibited growth arrest, but was absent in senescent cells. Conversely, the activity of glutathione disulfide reductase was greater in growth-arrested cultures than in mitotically active cells irrespective of oxygen tension. Glucose-6-phosphate dehydrogenase was lowest in log-phase cells exposed to different oxygen tensions for 24 h and in senescent cells. Both hypoxia and hyperoxia depressed selenium-dependent glutathione peroxidase activity in early passage cultures, while the activity of the enzyme progressively declined with increasing oxygen in senescent cells. The GSH S-transferase activity was unresponsive to changes in ambient oxygen tension in either young or senescent cultures. Manganese-containing superoxide dismutase (MnSOD) activity was unaffected by oxygen tension, but was elevated in young confluent cultures as compared with cultures in log-phase growth. MnSOD activity was significantly higher in senescent cultures than in early passage cultures and was also responsive to increased oxygen tension in senescent cultures. Copper-zinc-containing superoxide dismutases activity was not affected by oxygen tension or the passage of time, but it declined in senescent cultures.
Balin
Arthur K
AK
Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. akbalin@balin.com
Reimer
Richard J
RJ
Reenstra
Wende R
WR
Lilie
Steven M
SM
Leong
Ina
I
Sullivan
Katherine
K
Allen
Robert G
RG
D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D016922:Cellular Senescence / Q000187:drug effects*; D003300:Copper / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008345:Manganese / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
D000975:Antioxidants; D008345:Manganese; D003300:Copper; D005954:Glucosephosphate Dehydrogenase; D013482:Superoxide Dismutase; D005978:Glutathione; D015032:Zinc; D010100:Oxygen
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