Requirement of HIF-1 and insulin pathway to confer thermotolerance by chlorogenic acid in C elegans.

CARRANZA, A.; SARAGUSTI, AC; ASIS, R

Mar del Plata

Congreso; Reunión SAIB 2015; 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

In previous studies we demonstrated that chlorogenic acid (CGA) confers thermal stress resistance in C.elegans exposed to lethal temperature (37ºC). Its role in the stress resistance is not fully understood. The objective of this study was to investigate the molecular mechanism of CGA-induced thermal stress resistance in C. elegans. Here we have studied how DAF-2 insulin receptor pathway (IRP) (that regulates aging and stress) and HIF-1 pathway are involved in this CGA activity. Worms preincubated for 18h with Wortmannin or LY294002 (both PI3K inhibitors) shown a higher thermal resistance in the wild type N2 strain. DAF-16 is a forkhead transcription factor that transduces the effects of the IRP. The PI3K inhibition leads to induction of DAF16, which control several antioxidant and chaperone genes. PI3K inhibitors did not show activity in DAF16 mutant. However, CGA was active in DAF16 and DAF2 (insulin receptor) mutant. We have previously demonstrated that CGA preincubation increase the protein levels of HIF-1 and their activity in C. elegans. Herein we observed the HIF-1 induction by heat acclimation (25ºC) or cobalt ion preincubation conferred thermal stress resistance in N2 strain. Moreover, CGA was inactive in HIF-1 mutant whereas PI3K inhibitors kept their activities. These results indicate that CGA activity required HIF-1 pathway but no IGF pathway.