The effect of hypoxia on collagen synthesis in cultured 3T6 fibroblasts and its relationship to the mode of action of ascorbate.

When exposed to low oxygen tension, in the absence of added ascorbic acid 3T6 mouse fibroblast cultures in late log phase respond by increased lactate production and increased hydroxylation of proline in nascent collagen, which is paralleled by an increase in prolyl hydroxylase activity. After 6 h recovery from the anoxic stimulus, however, cultures still yield more prolyl hydroxylase than controls, but the effect on hydroxylation of nascent collagen has disappeared. These observations help to dissect the dual role of ascorbate which can stimulate hydroxylation both by increasing the amount of active enzyme and by a cofactor-like role; in addition, these observations may be relevant to wound healing.