title: Vitamin D Reduces Oxidative Stress-Induced Procaspase-3/ROCK1 Activation and MP Release by Placental Trophoblasts.
abstract: Increased microparticle (MP) shedding by placental trophoblasts contributes to maternal vascular inflammatory response and endothelial dysfunction in preeclampsia. Vitamin D has beneficial effects in pregnancy; however, its effect on trophoblast MP release has not been investigated.
  
  
  
  To investigate if vitamin D could protect trophoblasts from oxidative stress-induced MP release.
  
  
  
  Placental trophoblasts were isolated from uncomplicated and preeclamptic placentas. Effects of vitamin D on MP release induced by oxidative stress inducer CoCl2 were studied.
  
  
  
  Annexin V+ MPs were assessed by flow cytometry. Expression of caveolin-1, endothelial nitric oxide synthase (eNOS), procaspase-3, cleaved caspase-3, and Rho-associated coiled-coil protein kinase 1 (ROCK1) in trophoblasts and trophoblast-derived MPs were determined by Western blot.
  
  
  
  Trophoblasts from preeclamptic pregnancies released significantly more MPs than cells from uncomplicated pregnancies (P < 0.01). CoCl2-induced increase in MP release was associated with upregulation of caveolin-1 and downregulation of eNOS expression in trophoblasts (P < 0.05), which could be attenuated by 1,25(OH)2D3. Moreover, 1,25(OH)2D3 could also inhibit CoCl2-induced procaspase-3 cleavage and ROCK1 activation in trophoblasts. Consistently, CoCl2-induced upregulation of procaspase-3, cleaved caspase-3, and ROCK1 expression in trophoblast-derived MPs were also reduced in cells treated with 1,25(OH)2D3.
  
  
  
  Placental trophoblasts from preeclamptic pregnancies released more MP than cells from uncomplicated pregnancies. Oxidative stress-induced increase in MP shedding is associated with upregulation of caveolin-1 and downregulation of eNOS expression in placental trophoblasts. Inhibition of caspase-3 cleavage and ROCK1 activation, together with upregulation of eNOS expression, could be the potential cellular/molecular mechanism(s) of vitamin D protective effects on placental trophoblasts.
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.|Department of Physiology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors.forename: Xiuyue
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors.forename: David F
authors.initials: DF
authors.lastname: Lewis
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000187:drug effects* / Q000378:metabolism; D051242:Caveolin 1 / Q000187:drug effects / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011225:Pre-Eclampsia; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*; D055815:Young Adult; D054460:rho-Associated Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D014815:Vitamins; D003035:Cobalt; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D053148:Caspase 3; C018021:cobaltous chloride; D002117:Calcitriol