PMID- 12498736
OWN - NLM
STAT- MEDLINE
DCOM- 20030114
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 185
IP  - 3
DP  - 2002 Dec 15
TI  - Altered protein profile and possible hypoxia in the placenta of 
      2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed rats.
PG  - 197-206
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy causes 
      fetal death in many animal species. In an earlier study we observed alteration of 
      placental glucose kinetics at the same TCDD exposure level that resulted in fetal 
      death (Ishimura et al., Toxicol. Appl. Pharmacol. 178, 161-171, 2002). In the 
      present study, in order to identify the molecules that might explain the 
      alterations of placental function and the mechanism of fetal death, we used 
      two-dimensional gel electrophoresis (2D/E) to detect and identify placental 
      proteins whose amounts changed after exposure to TCDD and we examined the 
      expression properties of these proteins in the placenta during hypoxia by using 
      the uterine artery ligation model. Pregnant Holtzman rats were given a single 
      oral dose of 1600 ng TCDD/kg body wt or an equivalent volume of vehicle (control) 
      on gestational day (GD) 15 and placental tissue was collected on GD16 and GD20. 
      The 15,000 g supernatant fractions of placental homogenates from the control 
      group and TCDD-exposed group were subjected to the 2D/E analysis, and the protein 
      spots whose amounts had changed after exposure to TCDD were characterized by 
      amino acid sequence analysis. The amounts of heat shock protein 27 (Hsp27) and 
      beta-tropomyosin (beta-TM) in TCDD-exposed placentas tended to have increased on 
      GD16 and had increased significantly on GD20, and these changes were followed by 
      an approximately twofold increase in glyceraldehyde 3-phosphate dehydrogenase 
      (GAPDH) on GD20. Next, the uterine-artery ligation model was prepared on GD15, 
      and the hypoxic placentas were collected on GD20. Two-D/E analysis of the 15,000 
      g supernatant proteins of the placentas revealed an increased level of GAPDH but 
      not of other proteins, including Hsp27 and beta-TM. The results of this study 
      showed that the increase in GAPDH level during hypoxia previously observed in 
      endothelial cells occurs in the placenta and indicated that the TCDD-exposed 
      placentas were in a hypoxic state at the end of pregnancy. Finally, the results 
      of this study suggested the possibility that the increased incidence of fetal 
      death after exposure to TCDD was due to the placental hypoxia.
FAU - Ishimura, Ryuta
AU  - Ishimura R
AD  - Environmental Health Sciences Division, National Institute for Environmental 
      Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
FAU - Ohsako, Seiichiroh
AU  - Ohsako S
FAU - Kawakami, Takashige
AU  - Kawakami T
FAU - Sakaue, Motoharu
AU  - Sakaue M
FAU - Aoki, Yasunobu
AU  - Aoki Y
FAU - Tohyama, Chiharu
AU  - Tohyama C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (HSP27 Heat-Shock Proteins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hspb1 protein, rat)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Proteins)
RN  - 0 (Tropomyosin)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Female
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/biosynthesis
MH  - HSP27 Heat-Shock Proteins
MH  - *Heat-Shock Proteins
MH  - Hypoxia/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/biosynthesis
MH  - Placenta/drug effects/*metabolism
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Proteins/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Regional Blood Flow/physiology
MH  - Tropomyosin/biosynthesis
MH  - Uterus/blood supply
EDAT- 2002/12/25 04:00
MHDA- 2003/01/15 04:00
CRDT- 2002/12/25 04:00
PHST- 2002/12/25 04:00 [pubmed]
PHST- 2003/01/15 04:00 [medline]
PHST- 2002/12/25 04:00 [entrez]
AID - S0041008X02995396 [pii]
AID - 10.1006/taap.2002.9539 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2002 Dec 15;185(3):197-206. doi: 10.1006/taap.2002.9539.