Mammalian cardiac myocytes and neurons are conditioned by a period of hypoxia (low oxygen tension) to survive subsequent, more severe conditions of hypoxia. This adaptation process, known as hypoxic preconditioning (HP), has not been observed in invertebrates, leading Dasgupta et al. to investigate whether the nematode Caenorhabditis elegans exhibits features of HP. The authors exposed C. elegans to a 4-hour hypoxic episode, allowed the animals to recover, and then subjected them to a further 20 hours of hypoxia. This resulted in a much higher survival rate for these organisms than was observed in C. elegans that underwent 20-hour hypoxia without the earlier incubation. At least 8 hours of recovery time was needed after the initial hypoxic episode for protection to occur, which is consistent with late-phase HP in vertebrates. Microscopic analysis showed that the extent of hypoxia-induced pathology in the myocytes and neurons of C. elegans that had undergone HP was reduced compared with that in organisms without HP. Whereas C. elegans that had a loss-of-function mutation in ced-4 (which encodes a component of the C. elegans apoptosis pathway) did not exhibit HP after early hypoxia, C. elegans with mutants of other components of this pathway exhibited normal HP. These included C. elegans with mutations in ced-3, which encodes CED-3, a protein that is known to multimerize with CED-4 to form an active caspase. This suggests a nonapoptotic role for CED-4 in the establishment of HP. Together, these data suggest that HP does indeed occur in invertebrates and that C. elegans might serve as a useful model organism for the study of HP.
N. Dasgupta, A. M. Patel, B. A. Scott, C. M. Crowder, Hypoxic preconditioning requires the apoptosis protein CED-4 in C. elegans. Curr. Biol. 17, 1954-1959 (2007). [PubMed]