title: Glutathione transferase pi class 2 (GSTp2) protects against the cardiac deformities caused by exposure to PAHs but not PCB-126 in zebrafish embryos.
abstract: Glutathione transferases (GSTs) are phase II enzymes that detoxify a wide range of toxicants and reactive intermediates. One such class of toxicants is the ubiquitous polycyclic aromatic hydrocarbons (PAHs). Certain PAHs are known to cause developmental cardiac toxicity in fish. Herein, we explored the role of GST pi class 2 (GSTp2) in PAH- and PCB-induced cardiac toxicity in zebrafish (Danio rerio) embryos. We measured expression of GSTp2 in embryos exposed to individual and co-exposures of the PAHs benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), and fluoranthene (FL) as well as 3,3',4,4',5-pentachlorobiphenyl (PCB-126). GSTp2 mRNA expression was induced by exposure to BkF, BaP, PCB-126, and BaP+FL and BkF+FL co-exposure. A splice junction morpholino was then used to knockdown GSTp2 in developing zebrafish. GSTp2 knockdown exacerbated the toxicity caused by co-exposures to BkF+FL and BaP+FL. However, GSTp2 knockdown did not affect PCB-126 toxicity. These results further suggest that pi class GSTs serve a protective function against the synergistic toxicity caused by PAHs in developing zebrafish.
authors.affiliation: Nicholas School of the Environment, Duke University, Box 90328, Durham, North Carolina 27708, USA. lav3@duke.edu
authors.forename: Lindsey V T
authors.initials: LV
authors.lastname: Garner
authors.forename: Richard T
authors.initials: RT
authors.lastname: Di Giulio
mesh_terms: D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000201:enzymology; D047108:Embryonic Development / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D060172:Morpholinos / Q000008:administration & dosage / Q000235:genetics; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000145:classification / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D004965:Estrogen Antagonists; D060172:Morpholinos; D011084:Polycyclic Aromatic Hydrocarbons; D011078:Polychlorinated Biphenyls; D051549:Glutathione S-Transferase pi; C023035:3,4,5,3',4'-pentachlorobiphenyl