title: Increased ADAM10 expression in preeclamptic placentas is associated with decreased expression of hydrogen sulfide production enzymes.
abstract: Placental soluble fms-like tyrosine kinase 1 (sFlt1) release is increased in preeclampsia, which might be associated with increased shedding of Flt-1 through a disintegrin and metalloproteinase 10 (ADAM10). Here, we explored whether ADAM10 expression is regulated by hydrogen sulfide (H2S) in placenta. Pro- and active-ADAM10 expression were significantly increased in preeclamptic placentas and inversely correlated to H2S production enzymes cystathionine β-synthase and cystathionine γ-lyase expression. H2S significantly suppressed pro- and active-ADAM10 expression whilst inhibited sFlt-1 release. Knockdown of ADAM10 caused a decrease in sFlt-1 release. Our data suggest that dysregulation of H2S production may contribute to excessive Flt-1shedding in preeclampsia.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, PR China.
authors.forename: T
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Maternity and Child Health Hospital of Pudong New District, Shanghai, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Maternity and Child Health Hospital of Pudong New District, Shanghai, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Changhai Hospital, Shanghai, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, PR China. Electronic address: nixin@smmu.edu.cn.
authors.forename: X
authors.initials: X
authors.lastname: Ni
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: ADAM10; Hydrogen sulfide; Placenta; Preeclampsia; Soluble fms-like tyrosine kinase 1