Redox status of cultured fibroblasts. Possible relations with specific catabolic rates of proteoglycans.

Unlabelled: In cultured embyonic rat fibroblast the cytoplasmic NAD/NADH ratio was determined from the lactate/pyruvate ratio under acidic, hypoxic and lactic acid-rich conditions.

Results And Conclusions: The NAD/NADH ratio is reduced when the lactate concentration increases at pH 7.4 with and without hypoxia. At pH 6.6 this ratio is not reduced by lactate in normoxia: Conditions of aerobic glycolysis did not increase NADH. The NAD/NADH ratio was strongly lowered at pH 6.6 by lactate plus hypoxia. At low cell density this condition of hypoxic glycolysis is correlated with the increase of the specific activities of CS- and DS-proteoglycans (DS much greater than CS). But only the CS concentration was increased. Conditions of aerobic glycolysis at low cell density caused a moderate increase of both the specific activity and concentration of DS. The different regulation of the turnover of CS- and DS-proteoglycans is suggested to be based on their different synthetic capacities (CS greater than DS) on the one side and on the effect of specifically acting proteoglycanases on the other side. Maximal degradation of proteoglycans seems to be stimulated by NADH-activated proteases, supposedly thiol proteases. Lower degradation seems to be effectuated under non-reductive acidic conditions. Both these types of degradation seem stronger to affect DS-proteoglycan. Some neutral proteases seem stronger to affect CS-proteoglycan. Improved oxygen supply might reduce the CS concentration in proliferating tissue, such as in chronic inflammation, and thus reduce this process.