CIBICI, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina.
Instituto de Fisiología Biología Molecular y Neurociencias (IFIBYNE-CONICET-UBA), Buenos Aires, Argentina; Facultad de Agronomía, Universidad de Buenos Aires, Argentina.
Phytomedicine. 2020 Jan;66:153132. doi: 10.1016/j.phymed.2019.153132. Epub 2019 Nov 4.
Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and plant-derived food with antioxidant and protective activities against cell stress. Caenorhabditis elegans is a model organism particularly useful for understanding the molecular and biochemical mechanisms associated with aging and stress in mammals. In C. elegans, CGA was shown to improve resistance to thermal, while the underlying mechanisms that lead to this effect require further understanding.
The present study was conducted to investigate the underlying molecular mechanisms behind CGA response conferring thermotolerance to C. elegans.
Signaling pathways that could be involved in the CGA-induced thermotolerance were evaluated in C. elegans strains with loss-of-function mutation. CGA-induced thermotolerance required hypoxia-inducible factor HIF-1 but no insulin pathway. CGA exposition (1.4 µM CGA for 18 h) before thermal stress treatment increased HIF-1 levels and activity. HIF-1 activation could be partly attributed to an increase in radical oxygen species and a decrease in superoxide dismutase activity. In addition, CGA exposition before thermal stress also increased autophagy just as hormetic heat condition (HHC), worms incubated at 36 °C for 1 h. RNAi experiments evidenced that autophagy was increased by CGA via HIF-1, heat-shock transcription factor HSF-1 and heat-shock protein HSP-16 and HSP-70. In contrast, autophagy induced by HHC only required HSF-1 and HSP-70. Moreover, suppression of autophagy induction showed the significance of this process for adapting C. elegans to cope with thermal stress.
This study demonstrates that CGA-induced thermotolerance in C. elegans is mediated by HIF-1 and downstream, by HSF-1, HSPs and autophagy resembling HHC.
绿原酸（CGA）是一种广泛分布于植物和植物源性食品中的多酚，具有抗氧化和保护细胞免受应激的作用。秀丽隐杆线虫是一种特别适用于理解与哺乳动物衰老和应激相关的分子和生化机制的模式生物。在秀丽隐杆线虫中，CGA 被证明可以提高对热的抵抗力，但其导致这种效果的潜在机制仍需进一步理解。
本研究旨在探讨 CGA 提高秀丽隐杆线虫耐热性的潜在分子机制。
在秀丽隐杆线虫具有功能丧失突变的菌株中评估了可能参与 CGA 诱导耐热性的信号通路。CGA 诱导的耐热性需要缺氧诱导因子 HIF-1，但不需要胰岛素途径。在热应激处理前暴露于 CGA（1.4µM CGA 持续 18 小时）会增加 HIF-1 水平和活性。HIF-1 的激活部分归因于活性氧的增加和超氧化物歧化酶活性的降低。此外，在热应激前暴露于 CGA 还会增加自噬，就像应激性热条件（HHC）一样，将线虫在 36°C 下孵育 1 小时。RNAi 实验表明，CGA 通过 HIF-1、热休克转录因子 HSF-1 和热休克蛋白 HSP-16 和 HSP-70 增加自噬。相比之下，HHC 诱导的自噬仅需要 HSF-1 和 HSP-70。此外，抑制自噬诱导表明该过程对适应秀丽隐杆线虫应对热应激的重要性。
本研究表明，CGA 诱导的秀丽隐杆线虫耐热性是通过 HIF-1 介导的，下游通过 HSF-1、HSPs 和自噬介导，类似于 HHC。
