Effects of Oxidative Stress on Behavior, Physiology, and the Redox Thiol Proteome ofCaenorhabditis elegans

Abstract

Accumulation of reactive oxygen species has been implicated in various diseases and aging. However, the precise physiological effects of accumulating oxidants are still largely undefined. Here, we applied a short-term peroxide stress treatment to young Caenorhabditis elegans and measured behavioral, physiological, and cellular consequences. We discovered that exposure to peroxide stress causes a number of immediate changes, including loss in mobility, decreased growth rate, and decreased cellular adenosine triphosphate levels. Many of these alterations, which are highly reminiscent of changes in aging animals, are reversible, suggesting the presence of effective antioxidant systems in young C. elegans. One of these antioxidant systems involves the highly abundant protein peroxiredoxin 2 (PRDX-2), whose gene deletion causes phenotypes symptomatic of chronic peroxide stress and shortens lifespan. Applying the quantitative redox proteomic technique OxICAT to oxidatively stressed wild-type and prdx-2 deletion worms, we identified oxidation-sensitive cysteines in 40 different proteins, including proteins involved in mobility and feeding (e.g., MYO-2 and LET-75), protein translation and homeostasis (e.g., elongation factor 1 [EFT-1] and heat shock protein 1), and adenosine triphosphate regeneration (e.g., nucleoside diphosphate kinase). The oxidative modification of some of these redox-sensitive cysteines may contribute to the physiological and behavioral changes observed in oxidatively stressed animals.

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non‐cell‐autonomous stress response

“…Superoxides are converted to hydrogen peroxide by superoxide dismutases (SOD) followed by a conversion to water by catalases (CTL) or peroxiredoxins (PRDX) (Sies, 2014). The C. elegans genome encodes 5 different superoxide dismutases ( sod‐1 to sod‐5 ), three different catalases ( ctl‐1 to ctl‐3 ), and three peroxiredoxins that are named according to their homology to the mammalian peroxiredoxins, prdx‐2 , prdx‐3, and prdx‐6 (Doonan et al ., 2008; Olahova et al ., 2008; Kumsta et al ., 2011). …”

Interplay between redox and protein homeostasis

“…actin biogenesis 89 ) and CDC-48 (e.g., targeting of retro-translocated ERAD substrates 90 ). 91 So far, it is unknown if these oxidative-sensitive cysteines have an activating or inhibiting function. For the mammalian homolog of HSP-1, Hsc70, it could be shown that oxidation of an internal thiol through glutathione accelerated the Hsc70 activity in protein aggregate prevention in vitro.…”

“…95 C. elegans has also been used as a model for redox proteomic analysis and fluorescent biosensors. 15,91,96,97 Redox sensors…”

“…16,97 Taking advantage of this technique, oxidation sensitive cysteines in 40 different proteins were identified, that are involved in numerous biological pathways in worms. 91 One of these proteins is the chaperone HSP-1 (Hsc70 homolog) that is highly oxidized in aged animals. 16,91 The cytosolic redox proteome of C. elegans in general is more oxidized during development and during aging compared to the reproductive stage of young adults.…”

“…91 One of these proteins is the chaperone HSP-1 (Hsc70 homolog) that is highly oxidized in aged animals. 16,91 The cytosolic redox proteome of C. elegans in general is more oxidized during development and during aging compared to the reproductive stage of young adults. The ability to recover from an oxidative stress is linked to the lifespan extension.…”