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Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female zebrafish. 2019

Zhikuan Wang, and Guangyu Li, and Qin Wu, and Chunsheng Liu, and JianZhong Shen, and Wei Yan
College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.

Recently, several studies showed that microcystin-LR (MCLR) can accumulate and induce toxicity in kidney. However, the exact mechanism is unknown. The aim of this study was to explore the mechanism of MCLR-induced nephrotoxicity. To this end, adult zebrafish were exposed to MCLR (0, 1, 5 and 25 μg/L) for 60 days. Exposure to MCLR caused histopathological lesions, which were characterized by renal tubules filled with eosinophilic casts, abnormal renal tubules, intertubular space decrease, and blood infiltration in renal cells. RNA-Seq analysis indicated that exposure to MCLR significantly interfered with renal gene expressions, and these genes were enriched in various pathways, such as oxidative phosphorylation, cell cycle, and protein processing in endoplasmic reticulum, which were related to apoptosis. Furthermore, terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure induced renal cell apoptosis. In addition, negative changes of the reactive oxygen species (ROS) level as well as apoptotic-related gene, protein expressions and enzyme activities suggested that MCLR could induce production of ROS, subsequently triggering apoptosis via p53-bcl-2 and caspase-dependent pathway in the kidney of zebrafish. Therefore, it can be concluded that apoptosis is a primary case of MCLR-induced nephrotoxicity.

UI MeSH Term Description Entries
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D008387 Marine Toxins Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES. Marine Biotoxins,Phycotoxins
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D052998 Microcystins Cyclic heptapeptides found in MICROCYSTIS and other CYANOBACTERIA. Hepatotoxic and carcinogenic effects have been noted. They are sometimes called cyanotoxins, which should not be confused with chemicals containing a cyano group (CN) which are toxic. Cyanoginosins
D020869 Gene Expression Profiling The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell. Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays

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