Hypoxia tolerance

Stenzel-Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington GA, et al. 2003. Effect of ischaemic preconditioning on genomic response to cerebral ischaemia similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states. Lancet 362 1028. 

Hochachka PW, Buck LT, Doll CJ et al (1996) Unifying theory of hypoxia tolerance molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci USA 93 9493-9498... 

Conversion of pyruvate into ethanol is a variant of cytosolic fermentation, which occurs, for instance, in yeast and hypoxia-tolerant fish, such as crucian carp and goldfish (van Waarde et al. 1993 Lutz and Nilsson 1997). Ethanol... 

Figure 3.4. A simplified phylogenetic tree of the animal kingdom, modified from Knoll and Carroll (1999), with lineages containing notably hypoxia-tolerant species highlighted (bold type, gray boxes). Even casual analysis suggests that hypoxia tolerance probably arose independently multiple times within the animal kingdom and, perhaps more signficantly, the figure indicates that hypoxia tolerance is widely distributed.

In a first attempt at a synthesis of information in this research (Hochachka, 1986), a channel arrest component of a hypoxia tolerance theory postulated (i) that hypoxia tolerant cells would have an inherent low permeability (either low channel densities or low channel activities) and (ii) that they would sustain a further suppression of membrane permeability to ions when exposed to oxygen lack (further channel arrest by either suppression of channel densities or channel activities). Turtle liver cells display both of these characteristics (especially when compared to mammalian homologs) thus they clearly fit the classical definition of metabolic and channel arrest as two telling signatures of hypoxia tolerance. 

While rescue of protein synthesis in hypoxia sensitive mammalian cells does not seem feasible without oxygen, exactly such a rescue system seems available to hypoxia tolerant cells (Land and Hochachka, 1995). One underlying rescue mechanism appears to require the overproduction of key elongation factors such as EFla with sustained hypoxia, the latter is overexpressed and accumulates throughout the stress period. 

DNA MICROARRAYS PROBING GENE RESPONSES TO 02 LIMITATION IN HYPOXIA-TOLERANT SPECIES... 

From these studies, it is now possible to construct a generalized framework or working hypothesis for how hypoxia-tolerant cells respond to oxygen lack (figure 3.18). During the very early acute phases, a poorly understood hypoxia-sensing and signal transduction system orchestrates a series of molecular hypoxia defense processes, which include ... 

The acute or defense phase of hypoxia tolerance is considered to blend almost imperceptibly into a secondary series of processes in the literature these are variously termed immediate-early gene responses (Webster et al., 1993) or accli-matory expression adjustments (Hochachka and Somero, 1984). As the combined effect of these processes is to reactivate some mRNA translational capacities and probably to consolidate and stabilize the cell at strikingly reduced ATP turnover rates, we refer to these combined processes as a rescue phase for establishing hypoxia tolerance. The rescue phase includes (figure 3.18)... 

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