Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells

Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells

Benzo(a)pyrene (BaP), a cigarette smoke component, is metabolized to diol esters (BPDE) that bind to DNA and form mutagenic BPDE‐DNA adducts. BaP activates stress enzymes including stress‐activated protein kinase/jun kinase (MAPK8/9) in embryos, AMP‐activated protein kinase alpha1/2 subunits (PRKAA1...

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Published in:Molecular reproduction and development Vol. 77; no. 6; pp. 533 - 539
Main Authors: Xie, Yufen, Abdallah, Mazen E., Awonuga, Awoniyi O., Slater, Jill A., Puscheck, Elizabeth E., Rappolee, Dan A.
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2010
Wiley-Liss
Subjects:
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
Animals
Benzo(a)pyrene - metabolism
Benzo(a)pyrene - toxicity
Biological and medical sciences
Cells, Cultured
Enzyme Activation
Female
Humans
Inhibitor of Differentiation Protein 2 - metabolism
Medical sciences
Mice
Nicotiana - chemistry
Pregnancy
Protein Subunits - genetics
Protein Subunits - metabolism
Smoking - adverse effects
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Tobacco, tobacco smoking
Toxicology
Trophoblasts - cytology
Trophoblasts - drug effects
Trophoblasts - metabolism
Trophoblaste
Tobacco smoke
Benzopyrene
Fetal membrane
Cell death
Toxicity
Stem cell
Inhibition
Cell differentiation
Mutagen
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Summary:Benzo(a)pyrene (BaP), a cigarette smoke component, is metabolized to diol esters (BPDE) that bind to DNA and form mutagenic BPDE‐DNA adducts. BaP activates stress enzymes including stress‐activated protein kinase/jun kinase (MAPK8/9) in embryos, AMP‐activated protein kinase alpha1/2 subunits (PRKAA1/2) in somatic cells, and inhibits the proliferation of trophoblast cell lineages. The loss of transcription factor inhibitor of differentiation (ID)2 is required for the initial differentiation of mouse trophoblast stem cells (TSC) in implanting mouse embryo to produce the first placental hormone, chorionic sommatomammotropin (CSH)1. Here we demonstrate that BaP activates PRKAA1/2 and causes ID2 protein loss in TSC in a time‐ and dose‐dependent manner. Although PRKAA1/2 was activated at low BaP doses, PRKAA1/2‐dependent ID2 protein loss occurred at a dose that was similar to the threshold that results in a significant decrease in TSC accumulation and decreased fraction of proliferating TSC. This suggests a possible relationship between stress‐induced declines in cell accumulation and stem cell differentiation when BaP levels are high. The threshold BaP dose that induces significant ID2 loss is in the range of a 2–3 pack/day habit, suggesting that this mechanism may be involved with implantation failure in smoking women. Mol. Reprod. Dev. 77: 533–539, 2010. © 2010 Wiley‐Liss, Inc.
Bibliography:istex:149B6CA810292DBB1484547B12CC7DE806474261
ArticleID:MRD21178
NIH - No. R01 HD40972A
ark:/67375/WNG-V353WRGZ-8
National Institute of Child Health and Human Development
Yufen Xie and Mazen E. Abdallah contributed equally to this work.
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1040-452X
1098-2795
DOI:10.1002/mrd.21178