Limitation in availability of oxygen (hypoxia) is a stress important in both biomedical and environmental contexts. Mammals, as air breathers, have a limited capacity to withstand sustained exposure to hypoxia. By contrast, some aquatic animals, such as certain fishes, are routinely exposed and resistant to severe environmental hypoxia. Understanding the changes in gene expression in fishes exposed to hypoxic stress could reveal novel mechanisms of tolerance that may shed new light on hypoxia and ischemia in higher vertebrates.
The long-jaw mudsucker Gillichthys mirabilis is a hypoxia-tolerant species that inhabits estuaries along the coastline of central and southern California, where it lives in burrows that characteristically have low levels of dissolved oxygen.
We are exploiting DNA microarray technology to investigate the response of this euryoxic fish to prolonged (up to 6 d) hypoxia. The temporal patterning of these changes indicates that wide-scale reorganization of energy-consuming and ATP-generating pathways occurs in G. mirabilis when exposed to hypoxic stress.
Our expression profile suggests the following hypoxia survival strategy. First, in skeletal muscle, which accounts for approximately one-half of the mass of the organism, the major energy-requiring processes like protein synthesis and locomotion are shut down very rapidly after onset of hypoxia. Then after 24 h, a strong induction in the liver of genes needed for enhanced anaerobic ATP production and for gluconeogenesis occurs. Concurrently, cell growth and proliferation are suppressed, which may serve to divert important energy resources away from growth toward those metabolic processes more essential for hypoxia survival.
Our gene expression screens are complemented by proteomic, biochemical, and histological studies of physiological status.
Publications:
Fraser, E.J., Vieira de Mello, L., Ward, D., Rees, H.R., Williams, D., Gracey, A.Y., & Cossins, A.R. (2006) Hypoxia-inducible myoglobin expression in nonmuscle tissues. Proc. Natl. Acad. Sci. USA, 103, 2977-2981. PubMed.
Gracey, A.Y., Troll, J., & Somero, G.N. (2001) Hypoxia-induced expression profiling in the euryoxic fish Gillichthys mirabilis. Proc. Natl. Acad. Sci. USA, 94: 1993-1998. PubMed.