Activation of multidrug efflux transporter activity at fertilization in sea urchin embryos (Strongylocentrotus purpuratus).
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.
Hamdoun
Amro M
AM
Hopkins Marine Station, Stanford University, 120 Oceanview Boulevard, Pacific Grove, CA 93950, USA. hamdoun@stanford.edu
Cherr
Gary N
GN
Roepke
Troy A
TA
Epel
David
D
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001692:Biological Transport; D002453:Cell Cycle; D003524:Cyclosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005456:Fluorescent Dyes / Q000378:metabolism; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010802:Phylogeny; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D047270:Strongylocentrotus purpuratus / Q000187:drug effects / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D003524:Cyclosporins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011804:Quinolines; D014747:Vinblastine; C059141:verlukast; C070272:valspodar