Toxicity and metabolism of 3-bromopyruvate in Caenorhabditis elegans

In this study, we aimed to evaluate the toxic effects, changes in life span, and expression of various metabolism-related genes inCaenorhabditis elegans, using RNA interference (RNAi) and mutant strains, after 3-bromopyruvate (3-BrPA) treatment.C. elegans was treated with various concentrations of 3-BrPA on nematode growth medium (NGM) plates, and their survival was monitored every 24 h. The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction (qPCR). Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase (HK) genes. The average life span ofC. elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group.hxk-1,hxk-2, andhxk-3 were overexpressed after the treatment with 3-BrPA. After successfully interferinghxk-1,hxk-2, andhxk-3, the 50% lethal concentration (LC50) of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control. All thecyp35 genes tested were overexpressed, exceptcyp-35B3. The induction ofcyp-35A1 expression was most obvious. The LC50 values of the mutant strainscyp-35A1,cyp-35A2,cyp-35A4,cyp-35B3, andcyp-35C1 were lower than that of the control. Thus, the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes, and thecyp-35 family plays a key role in the metabolism of 3-BrPA.
Source: Journal of Zhejiang University. Science. B. - Category: Universities & Medical Training Source Type: research