Biomaterial Database

Benzo[a]pyrene effects on glycine N-methyltransferase mRNA expression and enzyme activity in Fundulus heteroclitus embryos. 2010

Xiefan Fang, and Wu Dong, and Cammi Thornton, and Kristine L Willett

Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, University, MS 38677, USA.

Benzo[a]pyrene (BaP) is a ubiquitous environmental polycyclic aromatic hydrocarbon (PAH) contaminant that is both a carcinogen and a developmental toxicant. We hypothesize that some of BaP's developmental toxicity may be mediated by effects on glycine N-methyltransferase (GNMT). GNMT is a mediator in the methionine and folate cycles, and the homotetrameric form enzymatically transfers a methyl group from S-adenosylmethionine (SAM) to glycine forming S-adenosylhomocysteine (SAH) and sarcosine. SAM homeostasis, as regulated by GNMT, is critically involved in regulation of DNA methylation, and altered GNMT expression is associated with liver pathologies. The homodimeric form of GNMT has been suggested as the 4S PAH-binding protein. To further study BaP-GNMT interactions, Fundulus heteroclitus embryos were exposed to waterborne BaP at 10 and 100mug/L and both GNMT mRNA expression and enzyme activity were determined. Whole mount in situ hybridization showed GNMT mRNA expression was increased by BaP in the liver region of 7, 10 and 14dpf F. heteroclitus embryos. In contrast to mRNA induction, in vivo BaP exposure decreased GNMT enzyme activity in 4, 10 and 14dpf embryos. However, in vitro incubations of adult F. heteroclitus liver cytosol with BaP did not cause decreased enzyme activity. In conclusion, BaP exposure altered GNMT expression, which may represent a new target pathway for BaP-mediated embryonic toxicities and DNA methylation changes.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D009865	Oocytes	Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).	Ovocytes,Oocyte,Ovocyte
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D001564	Benzo(a)pyrene	A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.	3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014874	Water Pollutants, Chemical	Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.	Chemical Water Pollutants,Landfill Leachate,Leachate, Landfill,Pollutants, Chemical Water
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic