Cytoskeletal remodeling via Rho GTPases during oxidative and thermal stress in Caenorhabditis elegans

Abstract

Biological systems are highly sensitive to changes in their environment. Indeed, the molecular basis of the environmental stress response suggests that the specialized stress responses share more commonalities than previously believed. Here, we used the nematode C. elegans to gain insight into the role of Rho signaling during two common environmental challenges, oxidative and thermal stress. In response to heat shock (HS), wild type (N2) worms demonstrated reduced viability which was rescued by genetic suppression of CDC42 and RHO-1. Visualization of F-actin by phalloidin-rhodamine underscored a strict correlation between the levels of F-actin following GTPase suppression and survival. Additionally, genetic ablation of OSG-1, a Guanine Nucleotide Exchange Factor (GEF) previously implicated in oxidative stress, was associated with constitutively lower levels of F-actin and increased mortality. However, upon an oxidative insult F-actin stability decreased in N2 worms, a rescue of this affect was observed in OSG-1 null worms, consistent with the resistance exhibited by these worms to oxidative stress (OS). Together these data suggest that during conditions of thermal or oxidative stress Rho signaling promotes vulnerability by altering actin dynamics. Thus, the stability of the actin cytoskeleton, in part through a conserved mechanism mediated by Rho signaling, is a crucial factor for the cell’s survival to environmental challenges.

Differential phosphorylation regulates the shear stress‐induced polar activity of Rho‐specific guanine nucleotide dissociation inhibitor α

“…Some studies suggested that the phosphorylation of RhoGDIα is a vital mechanism to regulate the spatial interaction of RhoGDIα with Rho GTPases (Hodgson et al, 2016;Shcherbakova et al, 2018). Rho GTPases signaling is influenced by the extracellular environment, and shear stress can mediate RhoGDIα expression and Rac1 activity (Patel et al, 2017;Qi et al, 2008). The role of specific phoshphorylations of RhoGDIα in the regulation of its activity under shear stress is investigated in the present study.…”

Bioadaptation of implants to In vitro and In vivo oxidative stress pathological conditions via nanotopography-induced FoxO1 signaling pathways to enhance Osteoimmunal regeneration

“…Upon activation by oxidative stress, Nrf2 translocates into the nucleus and binds to AREs, promoting the transcription of a wide variety of antioxidant genes [ 39 ]. Another potential mechanism is the Rho/Rho-kinase (ROCK) signaling pathway, which can modulate actin cytoskeleton organization in response to oxidative stress [ 40 , 41 ]. It was reported that activating Rho signaling partially restored the cell stiffness destroyed by oxidative stress and decreased the intracellular ROS level [ 42 ].…”

Involvement of the DAF‐16/FOXO Pathway in the Antioxidant Activity of the Jaboticaba (Myrciaria trunciflora) Extract against Various Stressors Using Caenorhabditis elegans

“…[33] These proteins could stabilize proteins that are being formed and remodel proteins that have suffered damage and are modified. [34] The sun naturally emits ultraviolet radiation, but a large part does not reach the atmosphere due to the ozone layer present around the Earth, this radiation can cause immuno-logical and skin damage, in the case of chronic exposure it can lead to irreversible damage and aging. [35] The concentration of 100 and 250 μg of GAE/mL of jaboticaba extract showed the ability to protect the nematodes against acute UV exposure on days 3, 5 and 7, while the concentration of 50 μg of GAE/mL showed these effects on days 5 and 7 (Figure 3D and E).…”