Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 159 (2015): 156-166, doi:10.1016/j.aquatox.2014.12.017.
Description:
Atlantic killifish (Fundulus heteroclitus) thrive in New Bedford Harbor (NBH), MA, highly contaminated with polychlorinated biphenyls (PCBs). Resident killifish have evolved tolerance to dioxin-like (DL) PCBs, whose toxic effects through the aryl hydrocarbon receptor (AhR) are well studied. In NBH, non-dioxin like PCBs (NDL PCBs), which lack activity toward the AhR, vastly exceed levels of DL congeners yet how killifish counter NDL toxic effects has not been explored. In mammals and fish, NDL PCBs are potent activators of ryanodine receptors (RyR), Ca2+ release channels necessary for a vast array of physiological processes. In the current study we compared the expression and function of RyR related pathways in NBH killifish with killifish from the reference site at Scorton Creek (SC, MA). Relative to the SC fish, adults from NBH displayed increased levels of skeletal muscle RyR1 protein, and increased levels of FK506-binding protein 12 kDa (FKBP12), an accessory protein essential for NDL PCB-triggered changes in RyR channel function. In accordance with increased RyR1 levels, NBH killifish displayed increased maximal ligand binding, increased maximal response to Ca2+ activation and increased maximal response to activation by the NDL PCB congener PCB 95. Compared to SC, NBH embryos and larvae had increased levels of mtor and ryr2 transcripts at multiple stages of development, and generations, while levels of serca2 were decreased at 9 days post-fertilization in the F1 and F2 generations. These findings suggest that there are compensatory and heritable changes in RyR mediated Ca2+ signaling proteins or potential signaling partners in NBH killifish.
Description:
Funding was provided through the NIEHS Superfund Research Program
UC Davis (INP and EBF; P42-ES004699) and Boston University (JJS and JVG; P42-ES007381).
Support was supplied via the UC Davis NHLBI Training Grant (T32-HL086350, EBF). Additional support came from NIEHS 1R01-ES014901, 1R01-ES017425, the UC Davis Center for Children’s Environmental Health (1P01-ES011269, U.S. Environmental Protection Agency Grant 8354320), and an unrestricted JB Johnson Foundation gift grant.
Description:
2015-12-19
Keywords:
Non-dioxin like PCBs
;
Ryanodine receptor
;
Fundulus heteroclitus
;
PCB Tolerance
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Format:
application/pdf
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