Physioxic human cell culture improves viability, metabolism, and mitochondrial morphology while reducing DNA damage

ABSTRACTMulticellular organisms balance oxygen delivery and toxicity by having oxygen pass through several barriers before cellular delivery. In human cell culture, these physiologic barriers are removed, exposing cells to higher oxygen levels. Human cells cultured in ambient air may appear normal,...

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Published in:The FASEB journal 2019-04, Vol.33 (4), p.5716-5728
Main Authors: Timpano, Sara, Guild, Brianna D., Specker, Erin J., Melanson, Gaelan, Medeiros, Philip J., Sproul, Shannon L. J., Uniacke, James
Format: Article
Language:English
Subjects:
Antioxidants - metabolism
Cell Line, Tumor
Cell Proliferation - genetics
Cell Survival - genetics
Cells, Cultured
DNA Damage - genetics
Humans
Mitochondria - genetics
Mitochondria - metabolism
Oxidation-Reduction
oxidative stress
Oxidative Stress - genetics
oxygen
Oxygen - metabolism
physioxia
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Summary:ABSTRACTMulticellular organisms balance oxygen delivery and toxicity by having oxygen pass through several barriers before cellular delivery. In human cell culture, these physiologic barriers are removed, exposing cells to higher oxygen levels. Human cells cultured in ambient air may appear normal, but this is difficult to assess without a comparison at physiologic oxygen. Here, we examined the effects of culturing human cells throughout the spectrum of oxygen availability on oxidative damage to macromolecules, viability, proliferation, the antioxidant and DNA damage responses, metabolism, and mitochondrial fusion and morphology. We surveyed 4 human cell lines cultured for 3 d at 7 oxygen conditions between 1 and 21% O2. We show that oxygen levels and cellular benefit are not inversely proportional, but the benefit peaks within the physioxic range. Normoxic cells are in a perpetual state of responding to damaged macromolecules and mitochondrial networks relative to physioxic cells, which could compromise an investigation. These data contribute to the concept of an optimal oxygen availability for cell culture in the physioxic range where the oxygen is not too high to reduce oxidative damage, and not too low for efficient oxidative metabolism, but just right: the Goldiloxygen zone.—Timpano, S., Guild, B. D., Specker, E. J., Melanson, G., Medeiros, P. J., Sproul, S. L. J., Uniacke, J. Physioxic human cell culture improves viability, metabolism, and mitochondrial morphology while reducing DNA damage. FASEB J. 33, 5716–5728 (2019). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201802279R