Gaseous Signaling Compounds (Hydrogen Sulfide and Nitric Oxide) and Their Relative Roles in Affecting Anaerobic HeLa 229 Cell Viability

Metabolic pathways supporting long-term anaerobic cell viability have not been identified. The effect NO and H 2 S pathway effectors have on HeLa 229 cell viability was measured after 10 days anaerobic incubation. The addition of arginine or xanthine (NO pathway precursors) consistently increased HeLa cell viability by 13.1- and 4.4-fold, respectively. Allopurinol, a xanthine oxidase inhibitor, also increased viability, as compared to control levels. In contrast, inhibition of iNOS by 1400W increased cell viability by 79-fold. Regarding the H 2 S pathway, precursor cysteine enhanced viability by 9.8-fold with the greatest number of viable cells measured in response to the presence of a H 2 S donor (GYY4137), or an inhibitor of glutathione synthesis, propargylglycine (40- and 85-fold, respectively). These results demonstrate that the constitutive level of cell viability after extended (10 days) growth without oxygen can be modulated by affecting NO or H 2 S generating pathways.