PMID- 31898444 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20201123 IS - 1862-1783 (Electronic) IS - 1673-1581 (Print) IS - 1673-1581 (Linking) VI - 21 IP - 1 DP - 2020 Jan. TI - Toxicity and metabolism of 3-bromopyruvate in Caenorhabditis elegans. PG - 77-86 LID - 10.1631/jzus.B1900370 [doi] AB - In this study, we aimed to evaluate the toxic effects, changes in life span, and expression of various metabolism-related genes in Caenorhabditis 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 of C. 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, and hxk-3 were overexpressed after the treatment with 3-BrPA. After successfully interfering hxk-1, hxk-2, and hxk-3, the 50% lethal concentration (LC(50)) of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control. All the cyp35 genes tested were overexpressed, except cyp-35B3. The induction of cyp-35A1 expression was most obvious. The LC(50) values of the mutant strains cyp-35A1, cyp-35A2, cyp-35A4, cyp-35B3, and cyp-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 the cyp-35 family plays a key role in the metabolism of 3-BrPA. FAU - Gu, Qiao-Ling AU - Gu QL AD - The Institute of Minority Physique and Health, Medical College of Northwest University for Nationalities, Lanzhou 730030, China. AD - Department of Microbiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541100, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Anesthesiology, First Hospital, Lanzhou University, Lanzhou 730000, China. FAU - Fu, Xi-Mei AU - Fu XM AD - Pathogen Biology Institute, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. FAU - Lu, Zhao-Lian AU - Lu ZL AD - Pathogen Biology Institute, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. FAU - Yu, Yao AU - Yu Y AD - Pathogen Biology Institute, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China. FAU - Chen, Gen AU - Chen G AD - Department of Microbiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541100, China. FAU - Ma, Rong AU - Ma R AD - The Institute of Minority Physique and Health, Medical College of Northwest University for Nationalities, Lanzhou 730030, China. FAU - Kou, Wei AU - Kou W AD - The Institute of Minority Physique and Health, Medical College of Northwest University for Nationalities, Lanzhou 730030, China. FAU - Lan, Yong-Mei AU - Lan YM AD - The Institute of Minority Physique and Health, Medical College of Northwest University for Nationalities, Lanzhou 730030, China. LA - eng PT - Journal Article PL - China TA - J Zhejiang Univ Sci B JT - Journal of Zhejiang University. Science. B JID - 101236535 RN - 0 (CYP35 protein, C elegans) RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Pyruvates) RN - 0 (RNA, Messenger) RN - 63JMV04GRK (bromopyruvate) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Animals MH - Caenorhabditis elegans/*drug effects/metabolism MH - Caenorhabditis elegans Proteins/genetics MH - Cytochrome P-450 Enzyme System/genetics MH - Hexokinase/genetics/physiology MH - Pyruvates/metabolism/*toxicity MH - RNA, Messenger/analysis PMC - PMC6964992 OTO - NOTNLM OT - 3-Bromopyruvate; Caenorhabditis elegans; Hexokinase; Cytochrome P450 COIS- Compliance with ethics guidelines: Qiao-ling GU, Yan ZHANG, Xi-mei FU, Zhao-lian LU, Yao YU, Gen CHEN, Rong MA, Wei KOU, and Yong-mei LAN declared that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed. EDAT- 2020/01/04 06:00 MHDA- 2020/11/24 06:00 PMCR- 2020/01/01 CRDT- 2020/01/04 06:00 PHST- 2020/01/04 06:00 [entrez] PHST- 2020/01/04 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.1631/jzus.B1900370 [doi] PST - ppublish SO - J Zhejiang Univ Sci B. 2020 Jan.;21(1):77-86. doi: 10.1631/jzus.B1900370.