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Glafenine-induced intestinal injury in zebrafish is ameliorated by μ-opioid signaling via enhancement of Atf6-dependent cellular stress responses.

Publication ,  Journal Article
Goldsmith, JR; Cocchiaro, JL; Rawls, JF; Jobin, C
Published in: Dis Model Mech
January 2013

Beside their analgesic properties, opiates exert beneficial effects on the intestinal wound healing response. In this study, we investigated the role of μ-opioid receptor (MOR) signaling on the unfolded protein response (UPR) using a novel zebrafish model of NSAID-induced intestinal injury. The NSAID glafenine was administered to zebrafish larvae at 5 days post-fertilization (dpf) for up to 24 hours in the presence or absence of the MOR-specific agonist DALDA. By analysis with histology, transmission electron microscopy and vital dye staining, glafenine-treated zebrafish showed evidence of endoplasmic reticulum and mitochondrial stress, with disrupted intestinal architecture and halted cell stress responses, alongside accumulation of apoptotic intestinal epithelial cells in the lumen. Although the early UPR marker BiP was induced with glafenine-induced injury, downstream atf6 and s-xbp1 expression were paradoxically not increased, explaining the halted cell stress responses. The μ-opioid agonist DALDA protected against glafenine-induced injury through induction of atf6-dependent UPR. Our findings show that DALDA prevents glafenine-induced epithelial damage through induction of effective UPR.

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Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

January 2013

Volume

6

Issue

1

Start / End Page

146 / 159

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Unfolded Protein Response
  • Stress, Physiological
  • Signal Transduction
  • Receptors, Opioid, mu
  • Oligopeptides
  • Intestines
  • Intestinal Mucosa
  • Heat-Shock Proteins
 

Citation

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Goldsmith, J. R., Cocchiaro, J. L., Rawls, J. F., & Jobin, C. (2013). Glafenine-induced intestinal injury in zebrafish is ameliorated by μ-opioid signaling via enhancement of Atf6-dependent cellular stress responses. Dis Model Mech, 6(1), 146–159. https://doi.org/10.1242/dmm.009852
Goldsmith, Jason R., Jordan L. Cocchiaro, John F. Rawls, and Christian Jobin. “Glafenine-induced intestinal injury in zebrafish is ameliorated by μ-opioid signaling via enhancement of Atf6-dependent cellular stress responses.Dis Model Mech 6, no. 1 (January 2013): 146–59. https://doi.org/10.1242/dmm.009852.
Goldsmith, Jason R., et al. “Glafenine-induced intestinal injury in zebrafish is ameliorated by μ-opioid signaling via enhancement of Atf6-dependent cellular stress responses.Dis Model Mech, vol. 6, no. 1, Jan. 2013, pp. 146–59. Pubmed, doi:10.1242/dmm.009852.
Journal cover image

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

January 2013

Volume

6

Issue

1

Start / End Page

146 / 159

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Unfolded Protein Response
  • Stress, Physiological
  • Signal Transduction
  • Receptors, Opioid, mu
  • Oligopeptides
  • Intestines
  • Intestinal Mucosa
  • Heat-Shock Proteins