Effects of chlorogenic acid on thermal stress tolerance in C. elegans via HIF-1, HSF-1 and autophagy

CARRANZA, ANDREA DEL VALLE; SARAGUSTI, ALEJANDRA; CHIABRANDO, GUSTAVO ALBERTO; CARRARI, FERNANDO; ASIS, RAMÓN

PHYTOMEDICINE

ELSEVIER GMBH

Año: 2020 vol. 66

0944-7113

Background: Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and plant-derived food withantioxidant and protective activities against cell stress. Caenorhabditis elegans is a model organism particularlyuseful for understanding the molecular and biochemical mechanisms associated with aging and stress inmammals. In C. elegans, CGA was shown to improve resistance to thermal, while the underlying mechanisms thatlead to this effect require further understanding.Purpose: The present study was conducted to investigate the underlying molecular mechanisms behind CGAresponse conferring thermotolerance to C. elegans.Methods and results: Signaling pathways that could be involved in the CGA-induced thermotolerance wereevaluated in C. elegans strains with loss-of-function mutation. CGA-induced thermotolerance required hypoxiainduciblefactor HIF-1 but no insulin pathway. CGA exposition (1.4 μM CGA for 18 h) before thermal stresstreatment increased HIF-1 levels and activity. HIF-1 activation could be partly attributed to an increase in radicaloxygen species and a decrease in superoxide dismutase activity. In addition, CGA exposition before thermalstress also increased autophagy just as hormetic heat condition (HHC), worms incubated at 36 °C for 1 h. RNAiexperiments evidenced that autophagy was increased by CGA via HIF-1, heat-shock transcription factor HSF-1and heat-shock protein HSP-16 and HSP-70. In contrast, autophagy induced by HHC only required HSF-1 andHSP-70. Moreover, suppression of autophagy induction showed the significance of this process for adapting C.elegans to cope with thermal stress.Conclusion: This study demonstrates that CGA-induced thermotolerance in C. elegans is mediated by HIF-1 anddownstream, by HSF-1, HSPs and autophagy resembling HHC.