Effects of Chlorogenic Acid on Thermal Stress Tolerance in C. Elegans via HIF-1, HSF-1 and Autophagy

SARAGUSTI, A. C.; ASIS, R; CHIABRANDO G. A.; CARRANZA, A.V; CARRARI, F

Congreso; Second Latin American Worm Meeting; 2020

Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and plant-derived food with antioxidant and protective properties against cell stress. Caenorhabditis elegans (C. elegans) is a model organism particularly useful for understanding the molecular and biochemical mechanisms associated with aging and stress. In C. elegans, incubation with CGA improve resistance to thermal stress, while the underlying mechanisms that lead to this effect required further understanding The present study was conducted to investigate the underlying molecular mechanisms behind CGA?s effect in conferring thermotolerance to C. elegans (Di Paola Naranjo et al., 2016).We evaluated signaling pathways that could be involved in the CGA-inducedthermotolerance in C. elegans strains with loss-of-function mutation. CGA-induced thermotolerance required hypoxia-inducible factor HIF-1, but not insulin pathway. CGA exposition before thermal stress treatment increased HIF-1 concentration and activity.HIF-1 activation could be partly attributed to an increase in radical oxygen species and a decrease in superoxide dismutase activity. Moreover, CGA exposition before thermal stress also increased autophagy in the same way as hormetic heat condition (HHC) (worms incubated at 36 ºC/ 1 h). RNAi experiments evidenced that autophagy was increased by CGA via HIF-1, heat-shock transcription factor HSF-1 and heat-shock proteins HSP-16 and HSP-70. Interesting, suppression of autophagy showed the importance of this process for C. elegans to overcome thermal stress.This study demonstrated that HIF-1 is mediating CGA-induced thermotolerance, anddownstream, thermotolerance is mediated by HSF, HSP and autophagy, as is the case in HHC.