Activation of multidrug efflux transporter activity at fertilization in sea urchin embryos (Strongylocentrotus purpuratus)
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This study presents functional and molecular evidence for acquisition of multidrug transporter-mediated efflux activity as a consequence of fertilization in the sea urchin. Sea urchin eggs and embryos express low levels of efflux transporter genes with homology to the multidrug resistance associated protein (mrp) and permeability glycoprotein (p-gp) families of ABC transporters. The corresponding efflux activity is low in unfertilized eggs but is dramatically upregulated within 25 min of fertilization; the expression of this activity does not involve de novo gene expression and is insensitive to inhibitors of transcription and translation indicating activation of pre-existing transporter protein. Our study, using specific inhibitors of efflux transporters, indicates that the major activity is from one or more mrp-like transporters. The expression of activity at fertilization requires microfilaments, suggesting that the transporters are in vesicles and moved to the surface after fertilization. Pharmacological inhibition of mrp-mediated efflux activity with MK571 sensitizes embryos to the toxic compound vinblastine, confirming that one role for the efflux transport activity is embryo protection from xenobiotics. In addition, inhibition of mrp activity with MK571 alone retards mitosis indicating that mrp-like activity may also be required for early cell divisions.
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Based on inhibition characteristics, Sp-ABCB1 accounts for less of the embryo's calcein efflux activity than Sp-ABCC9A.
“Based on inhibition characteristics, Sp-ABCB1 accounts for less of the embryo's observed calcein efflux activity than Sp-ABCC9A (Hamdoun et al., 2004).”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Hamdoun et al., 2004
The main xenobiotic efflux in early sea urchin embryos is an MK-571 sensitive MRP-like activity.
“The main xenobiotic efflux in early embryos is an MK-571 sensitive MRP-like efflux activity (Hamdoun et al., 2004)”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Hamdoun et al., 2004
Some defense gene products may be packaged into eggs during oogenesis to provide adequate defense during early cleavage stages.
“Some defense gene products may be packaged into eggs during oogenesis to provide adequate defense during early cleavage stages when divisions are rapid and nucleus:cytoplasm ratios are low (Epel, 2003;Giudice et al., 1999;Hamdoun et al., 2004), a period in which gene expression is unlikely to result in efficient upregulation of protein concentration.”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Hamdoun et al., 2004
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Self-citation
- Authors
- Hamdoun, A. M., Cherr, G. N., Roepke, T. A., & Epel, D.
- Affiliations
- Hopkins Marine Station (US)
- University of California, Davis (US)
- Corresponding author
- Hamdoun, Amro M.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 276
- Issue
- 2
- Pages
- 452-462
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2143787420
- Cited by
- 91
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 10 · 2015: 4 · 2014: 11 · 2013: 5 · 2012: 9
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3150 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Commerce (R/CZ-182)
- National Oceanic and Atmospheric Administration
- California Sea Grant, University of California, San Diego
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD071131)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- multidrug efflux transporter, fertilisation (biology), sea urchin embryo, Strongylocentrotus purpuratus, multidrug resistance-associated protein, P-glycoprotein, ABC transporters, MK571, F-actin, mitosis
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Biological Transport, Cell Cycle, Cyclosporins, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Fertilization, Fluorescent Dyes, Male, Actin Cytoskeleton, Oocytes, Phylogeny, Propionates, Quinolines, Vinblastine, ATP-Binding Cassette, Sub-Family C Proteins, Strongylocentrotus purpuratus
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