Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

Abstract

The mechanisms underlying oxidative stress (OS) resistance are not completely clear. Caenorhabditis elegans (C. elegans) is a good organism model to study OS because it displays stress responses similar to those in mammals. Among these mechanisms, the insulin/IGF-1 signaling (IIS) pathway is thought to affect GABAergic neurotransmission. The aim of this study was to determine the influence of heat shock stress (HS) on GABAergic activity in C. elegans. For this purpose, we tested the effect of exposure to picrotoxin (PTX), gammaaminobutyric acid (GABA), hydrogen peroxide, and HS on the occurrence of a shrinking response (SR) after nose touch stimulus in N2 (WT) worms. Moreover, the effect of HS on the expression of UNC-49 (GABA A receptor ortholog) in the EG1653 strain and the effect of GABA and PTX exposure on HSP-16.2 expression in the TJ375 strain were analyzed. PTX 1 mM-or H 2 O 2 0.7 mM-exposed worms displayed a SR in about 80 % of trials. GABA exposure did not cause a SR. HS prompted the occurrence of a SR as did PTX 1 mM or H 2 O 2 0.7 mM exposure. In addition, HS increased UNC-49 expression, and PTX augmented HSP-16.2 expression. Thus, the results of the present study suggest that oxidative stress, through either H 2 O 2 exposure or application of heat shock, inactivates the GABAergic system, which subsequently would affect the oxidative stress response, perhaps by enhancing the activity of transcription factors DAF-16 and HSF-1, both regulated by the IIS pathway and related to hsp-16.2 expression.

Carotenoids from mamey (Pouteria sapota) and carrot (Daucus carota) increase the oxidative stress resistance of Caenorhabditis elegans

“…C. elegans exhibits defense mechanisms against oxidative stress similar to those of humans, such as antioxidant enzymes, glutathione system, and stress response signaling pathways [ 11 ]. A key regulator of the oxidative stress response is DAF-16, a forkhead class transcription factor homologous to the mammal FOXO protein family, which is regulated by the insulin/IGF-1 signaling (IIS) pathway [ 35 , 43 ].…”

“…In C. elegans , the IIS comprises an insulin/IGF-1 receptor (DAF-2), which regulates the activity of a phosphorylation cascade that modulates DAF-16 [ 45 , 46 ]. Under normal conditions, the IIS pathway downregulates the DAF-16 activity by preventing its translocation into the nucleus [ 11 ]. Environmental conditions such as stress, heat, nutrient depletion, heavy metals, and ultraviolet irradiation stimulate DAF-16 translocation into the nucleus, activating the expression of genes involve in the oxidative stress resistance and longevity [ 12 ].…”

“…Environmental contaminants, such as sunlight, smoke, ozone, and herbicides, are sources of reactive oxygen species (ROS). The overproduction of ROS could result in oxidative stress and oxidative damage to proteins, DNA, and membrane lipids [ 4 , 11 ]. The oxidative stress occurs when the balance between pro-oxidant and antioxidant compound is broken [ 12 ].…”

“…The oxidative stress occurs when the balance between pro-oxidant and antioxidant compound is broken [ 12 ]. The oxidative stress is associated with premature aging and development and progression of chronic diseases such as diabetes, atherosclerosis, Parkinson's, Alzheimer's, and Huntington's disease, and cancer [ 11 , 13 ]. Carotenoids play a major role in the cell protection against oxidative stress-induced by ROS, reactive nitrogen species (RNS), and lipid peroxides via its singlet oxygen-quenching activity and free radical-scavenging activity [ 1 ].…”