Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans

Abstract

Oxygen deprivation has a role in the pathology of many human diseases. Thus it is of interest in understanding the genetic and cellular responses to hypoxia or anoxia in oxygen-deprivation-tolerant organisms such as Caenorhabditis elegans. In C. elegans the DAF-2/DAF-16 pathway, an IGF-1/insulin-like signaling pathway, is involved with dauer formation, longevity, and stress resistance. In this report we compared the response of wild-type and daf-2(e1370) animals to anoxia. Unlike wild-type animals, the daf-2(e1370) animals have an enhanced anoxia-survival phenotype in that they survive long-term anoxia and hightemperature anoxia, do not accumulate significant tissue damage in either of these conditions, and are motile after 24 hr of anoxia. RNA interference was used to screen DAF-16-regulated genes that suppress the daf-2(e1370)-enhanced anoxia-survival phenotype. We identified gpd-2 and gpd-3, two nearly identical genes in an operon that encode the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. We found that not only is the daf-2(e1370)-enhanced anoxia phenotype dependent upon gpd-2 and gpd-3, but also the motility of animals exposed to brief periods of anoxia is prematurely arrested in gpd-2/3(RNAi) and daf-2(e1370);gpd-2/3(RNAi) animals. These data suggest that gpd-2 and gpd-3 may serve a protective role in tissue exposed to oxygen deprivation.

Anoxia-Induced Suspended Animation in Caenorhabditis elegans

“…The ability to survive longer bouts of anoxia depends upon developmental stage, growth temperature, diet, genotype and fertility; these factors will be elaborated on further in this chapter. In general, C. elegans are sensitive to anoxia (and hypoxia) if the temperature during exposure is increased (Ex: 28°C instead of 20°C) or if the duration of anoxia exposure is increased from one to three days (Mendenhall et al, 2006;Scott et al, 2002). After non-lethal exposures to anoxia the animals will resume biological processes such as cell division, development, eating, movement, and offspring production.…”

“…If so, the additional energy expenditure while swimming in liquid media may compromise anoxia tolerance. While adult hermaphrodites are anoxia-tolerant the survival rate plummets as the duration of anoxia is lengthened (Mendenhall et al, 2006;Mendenhall et al, 2009;Padilla et al, 2002). The 1-day old adult has a markedly decreased survival rate (4.7%) in long-term anoxia, defined as a 72 hour or more anoxia exposure at 20˚C, demonstrating that there is an anoxia survival limitation (Mendenhall et al, 2006).…”

“…While adult hermaphrodites are anoxia-tolerant the survival rate plummets as the duration of anoxia is lengthened (Mendenhall et al, 2006;Mendenhall et al, 2009;Padilla et al, 2002). The 1-day old adult has a markedly decreased survival rate (4.7%) in long-term anoxia, defined as a 72 hour or more anoxia exposure at 20˚C, demonstrating that there is an anoxia survival limitation (Mendenhall et al, 2006). The anoxia-survival limitation is taken advantage of to identify genetic mutations that lead to anoxia sensitivity (mutants that cannot survive 24 hours of anoxia) and anoxia tolerance (mutants that can survive long-term anoxia, > 3 days of anoxia).…”

“…The length of time animals remain active after the onset of anoxia varies among C. elegans strains. The majority of wild-type adults cease movement within 8 hours of the onset of anoxia (Mendenhall et al, 2006). However, the daf-2(e1370) animal, which is a long-term anoxia tolerant mutant strain and carries a reduction-offunction mutation in the insulin-like receptor (see section 6 below), will delay entering into suspended animation as demonstrated by observable movement after 24 hours of anoxia.…”

Non‐apoptotic cell death in Caenorhabditis elegans

“…Prolonged anoxia causes necrosis in all tissues of the worm, evident by the accumulation of propidium iodide-stained necrotic cells (Menuz et al, 2009). Specific daf-2 mutants are highly resistant to long-term anoxia, and this resistance is mediated by two glycolytic enzymes (glyceraldehyde-3-phosphate dehydrogenases) encoded by the genes gpd-2 and gpd-3 (Mendenhall et al, 2006).…”