Activation of Stress Response Pathways of C. elegans by Multiple Types of Stress
Dr. Jeremy M. Van Raamsdonk, Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute
Dr. Megan M. Senchuk, Van Andel Research Institute
The mechanism by which organisms age is largely unknown, but many studies suggest that ageing is related to stress. In order to understand the relationship between stress and ageing, we studied the mechanisms by which organisms respond to different stressors. In C. elegans, the activation of stress response pathways can be easily observed through the use of fluorescent reporters. Here, we used a series of fluorescent reporter strains to determine which types of stress can activate each different stress response pathway, and to define the optimal stress conditions for maximum activation of each reporter strain. We examined the following stress reporter pathways: the heat shock response/cytoplasmic unfolded protein response (Phsp-16.2::GFP), mitochondrial unfolded protein response (Phsp-6::GFP), endoplasmic reticulum unfolded protein response (Phsp-4::GFP), the SKN-1 mediated oxidative stress response (Pgst-4::GFP, Pgcs-1::GFP), hypoxia response (Pnhr-57::GFP), and the DAF-16 mediated stress response (Pdaf-16::daf-16;GFP, Psod-3::GFP). Each of these fluorescent reporter strains was then exposed to eight different types of stress: heat stress, cold stress, osmotic stress, anoxia, oxidative stress, starvation, endoplasmic reticulum stress, and bacterial pathogenic stress. We found that all of the stress response pathways are activated by multiple types of stress with the exception of the mitoUPR. Similarly, most types of stress activated multiple stress response pathways. These data have subsequently been used to study how the ability to respond to stress changes as organisms age.
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