title: Change of genes in calcium transport channels caused by hypoxic stress in the placenta, duodenum, and kidney of pregnant rats.
abstract: Preeclampsia is a pregnancy-specific disease characterized by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. In this study, we induced hypoxic stress in rats during pregnancy to reproduce physiological conditions associated with preeclampsia. The maternal weight of hypoxic pregnant rats was lower than that of normoxic animals. The level of calcium ions were also increased in urine collected from the hypoxic animals. In contrast, urinary concentrations of sodium, chloride, and potassium ions declined in hypoxic rats, and developed to proteinuria. The expression of genes known as two biomarkers, sFLT1 (for preeclampsia) and HIF-1alpha (for hypoxia), were highly induced in the placenta, duodenum, and kidney by hypoxic stress. The overexpression of sFLT1 and HIF-1alpha demonstrated that our experimental conditions closely mimicked ones that are associated with preeclampsia. In the present study, we measured the expression of calcium transporters (TRPV5, TRPV6, PMCA1, NCKX3, NCX1, and CaBP-9k) in the placenta, duodenum, and kidney under hypoxic conditions on Gestational Day 19.5 in rats. Placental TRPV5, TRPV6, and PMCA1 expression was up-regulated in the hypoxic rats, whereas the levels of NCX1 and CaBP-9k were unchanged. In addition, NCKX3 expression was increased in the placenta of hypoxic rats. Duodenal expression of CaBP-9k, TRPV5, TRPV 6, and PMCA1 was decreased in the hypoxic rats, whereas levels of NCXs were not altered. Renal expression of NCKX3 and TRPV6 was increased, whereas NCX1 was decreased in the hypoxic rats compared to the normoxic controls. Taken together, these results indicate that physiological changes observed in the hypoxic rats were similar to ones associated with preeclampsia. Expression of calcium transport genes in the placenta, duodenum, and kidney perturbed by hypoxic stress during pregnancy may cause calcium loss in the urine, and thereby induce calcium-deficient characteristics of preeclampsia.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Yang
authors.forename: Beum-Soo
authors.initials: BS
authors.lastname: An
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C511590:Slc24a3 protein, rat; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; C120776:TRPV6 channel; C110374:sodium-calcium exchanger 1; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D053499:Plasma Membrane Calcium-Transporting ATPases; C506955:Atp2b1 protein, rat