Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA

Erika B. Fritsch, John J. Stegeman, Jared V. Goldstone, Diane E. Nacci, Denise Champlin, Saro Jayaraman, Richard E Connon, Isaac N Pessah

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 12kDa (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.

Original languageEnglish (US)
Pages (from-to)156-166
Number of pages11
JournalAquatic Toxicology
Volume159
DOIs
StatePublished - Feb 1 2015

Fingerprint

Fundulidae
ryanodine receptors
Fundulus heteroclitus
Ryanodine Receptor Calcium Release Channel
Polychlorinated Biphenyls
polychlorinated biphenyls
PCB
harbor
dioxins
hydrocarbons
protein
calcium
Aryl Hydrocarbon Receptors
receptors
Dioxins
Poisons
muscle protein
dioxin
fish
skeletal muscle

Keywords

  • Fundulus heteroclitus
  • Non-dioxin like PCBs
  • PCB tolerance
  • Ryanodine receptor

ASJC Scopus subject areas

  • Aquatic Science
  • Health, Toxicology and Mutagenesis

Cite this

Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA. / Fritsch, Erika B.; Stegeman, John J.; Goldstone, Jared V.; Nacci, Diane E.; Champlin, Denise; Jayaraman, Saro; Connon, Richard E; Pessah, Isaac N.

In: Aquatic Toxicology, Vol. 159, 01.02.2015, p. 156-166.

Research output: Contribution to journalArticle

Fritsch, Erika B. ; Stegeman, John J. ; Goldstone, Jared V. ; Nacci, Diane E. ; Champlin, Denise ; Jayaraman, Saro ; Connon, Richard E ; Pessah, Isaac N. / Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA. In: Aquatic Toxicology. 2015 ; Vol. 159. pp. 156-166.
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AU - Goldstone, Jared V.

AU - Nacci, Diane E.

AU - Champlin, Denise

AU - Jayaraman, Saro

AU - Connon, Richard E

AU - Pessah, Isaac N

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