title: Hydrogen sulfide inhibits Na+ uptake in larval zebrafish, Danio rerio.
abstract: The present study investigated the role of hydrogen sulfide (H2S) in regulating Na(+) uptake in larval zebrafish, Danio rerio. Waterborne treatment of larvae at 4 days post-fertilization (dpf) with Na2S or GYY-4137 (chemicals known to generate H2S) significantly reduced Na(+) uptake. Exposure of larvae to water enriched with NaCl (1 mM NaCl) caused a pronounced reduction in Na(+) uptake which was prevented by pharmacological inhibition of cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE), two key enzymes involved in the endogenous synthesis of H2S. Furthermore, translational gene knockdown of CSE and CBSb significantly increased the basal rate of Na(+) uptake. Waterborne treatment with Na2S significantly decreased whole-body acid excretion and reduced Na(+) uptake in larval zebrafish preexposed to acidic (pH 4.0) water (a condition shown to promote Na(+) uptake via Na(+)-H(+)-exchanger 3b, NHE3b). However, Na2S did not affect Na(+) uptake in larvae depleted of NHE3b-containing ionocytes (HR cells) after knockdown of transcription factor glial cell missing 2 (gcm2) in which Na(+) uptake occurs predominantly via Na(+)-Cl(-) co-transporter (NCC)-containing cells. These observations suggest that Na(+) uptake via NHE3b, but not NCC, is regulated by H2S. Whole-mount immunohistochemistry demonstrated that ionocytes expressing NHE3b also express CSE. These data suggests a physiologically relevant role of H2S as a mechanism to lower Na(+) uptake in zebrafish larvae, probably through its inhibitory action on NHE3b.
authors.affiliation: Department of Biology, University of Ottawa, 30 Marie Curie, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kumai
authors.forename: Cosima S
authors.initials: CS
authors.lastname: Porteus
authors.forename: Raymond W M
authors.initials: RW
authors.lastname: Kwong
authors.forename: Steve F
authors.initials: SF
authors.lastname: Perry
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008190:Lyases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012869:Skin Absorption; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D013447:Sulfites / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013447:Sulfites; D014157:Transcription Factors; D029961:Zebrafish Proteins; C501172:gcm2 protein, zebrafish; D012964:Sodium; D008190:Lyases; D003541:Cystathionine beta-Synthase; C019965:cystathionine beta-lyase; C025026:sodium sulfite; D006862:Hydrogen Sulfide