Chlorogenic acid confers thermal stress resistance in Caenorhabditis elegans by a mechanism that requires HIF-1

SARAGUSTI A.; CARRANZA A.; DI PAOLA NARANJO R.D.; GUSTAVO A. CHIABRANDO; ASIS RAMÓN

Rosario

Congreso; L Reunión Anual de la Sociendad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

In previous studies, we demonstrated that tomato extracts confer thermal stress resistance in C. elegans, where chlorogenic acid (CGA) resulted their main bioactive compound. CGA is one of the most abundant polyphenol in the human diet with biological activities such as antioxidant and anticarcinogenic. Nevertheless, its role in the stress resistance in C. elegans is not fully understood. The objective of this study was to investigate the molecular mechanism of CGA-induced thermal stress resistance in C. elegans. Synchronized adult were incubated with different doses of CGA (5000, 500 and 50 ng/mL) at 20°C for 18 h; and enhanced heat tolerance (increase in survival) was observed in wild-type (N2) worms subjected to heat stress (37°C for 6 h). In contrast, the HIF-1 (hypoxia inducible factor) loss of-function strain (ZG31) did not show significant increase in heat tolerance. The protein levels of HIF-1 in adult worms were evaluated after CGA (5000 ng/mL) incubation at 20°C for 18 h, and significant increase in the levels of HIF-1 was evidenced. In addition, the analysis of the expression of two HIF-1 target genes (F22B5.4 and K10H10.2) showed significant increase in mRNA levels after incubation. We conclude that HIF-1 is required for the thermal stress resistance conferred by CGA in C. elegans. Likewise, CGA produces an increment in HIF-1 protein levels and HIF-1 target genes.