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[2837] Hyperoxic Responses in C. elegans.

 

Farhang Payvar, Andrew DeMatteo, and Tom Hazinski. Department of Pediatrics, Vanderbilt University Medical School, Nashville, TN, 37232.

 

Sunday, may 14, 2000, 2:30 PM, Rom 304

Poster Symposium: Oxidant/Antioxidants: Brain, Lungs, and Basic Mechanisms (2:30 PM-4:30 PM)

 

Objective: To understand the genetic events that are triggered by hyperoxia and how they might differ from oxidative stress per se.

 

Background: Hyperoxia can influence gene expression by transcriptional (JCI 96:2083-2089, 1995) and/or post-transcriptional mechanisms leading directly or indirectly to oxidant stress (OS). The details of these complex physiological processes can be difficult to determine in mammalian model systems. However, because the responses to these stimuli are likely to be universal properties of all multi-cellular organisms, it can be studied in the nematode Caenorhabditis elegans. C. elegans is an organism whose genome is essentially sequenced and is amenable to both forward and reverse genetics. Moreover, the animals demonstrate phenotypic responses to a variety of oxidative stress inducers.

 

Design/Methods: We exposed the wild-type (N2) strain of C. elegans to 3.5 days of hyperoxia (95% oxygen) either alone or in combination to varying concentration of sodium nitroprusside (NP), an OS inducer. We measured the survival rates under each experimental condition, and calculated the LD50 for NP treatment with and without hyperoxia.

 

Results: We found that survival was reduced by NP (LD50 6.4 mM) but not by hyperoxia. However, hyperoxia decreased the LD50 for NP to 2.2 mM. This ~ 3-fold increase in NP sensitivity suggests interaction between hyperoxia and NP signaling pathways.

In addition, we performed similar experiments in a C. elegans strains bearing mutations in the daf-2 (insulin-like receptor) gene. At permissive temperatures, this strain shows an increased tolerance to many forms of OS including hyperoxia. With this mutant strain, we found increased sensitivity to NP, and a reduced interaction between hyperoxia and NP, suggesting that in wild type animals, DAF-2 activity is essential for maximal protection against NP or combination of hyperoxia and NP.

 

Conclusions: We conclude that: 1) the genetic events which mediate the effects of hyperoxia are, at least in part, distinct from those for NP in C. elegans; and 2) C. elegans offers a unique opportunity to elucidate the specific genes and mechanisms responsible for physiological action of oxygen and OS inducers (Supported by HL56636).