Document Detail


3,5,3'-Triiodothyronine down-regulates Fas and Fas ligand expression and suppresses caspase-3 and poly (adenosine 5'-diphosphate-ribose) polymerase cleavage and apoptosis in early placental extravillous trophoblasts in vitro.
MedLine Citation:
PMID:  15292350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study was conducted to determine whether T(3) receptor exists in early placental extravillous trophoblasts (EVTs) and evaluate the influence of T(3) on Fas/Fas ligand expression, caspase-3, and poly (ADP-ribose) polymerase (PARP) cleavage and apoptosis in cultured early placental EVTs. EVTs with invasive phenotype, isolated from normal placental explants from early pregnancy through preincubation on human fibronectin-coated dishes and exhibited cytokeratin 7 and human placental lactogen immunopositive staining, were cultured in the absence or presence of T(3) (10(-7) to 10(-9) m). The presence of T(3) receptor in cultured EVTs was examined by immunocytochemistry, RT-PCR, and Southern blot analysis. Fas sensitivity was determined by treating the cells with an agonistic Fas antibody. Apoptosis was assessed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, flow cytometry, and Hoechst nuclear staining. Fas and Fas ligand expression and caspase-3 and PARP cleavage were evaluated by immunocytochemistry. Early placental EVTs expressed a 212-bp c-erb Abeta1 transcript and the T(3) receptor protein and exhibited significant levels of apoptosis in culture. Treatment with T(3) reduced the expression of Fas and Fas ligand as well as cleavage of caspase-3 and PARP and suppressed apoptosis in cultured EVTs. Although addition of agonistic Fas antibody increased apoptosis in these cells, this response was markedly attenuated by the presence of T(3). These results demonstrate that T(3) receptor is present in early placental EVTs and that T(3) suppresses apoptosis by down-regulating the expression of Fas and Fas ligand. These findings are consistent with the hypothesis that T(3) promotes EVT invasion to the decidua by suppressing apoptosis in early pregnancy.
Authors:
Jovelle B Laoag-Fernandez; Hiroya Matsuo; Homare Murakoshi; Anna Lissa Hamada; Benjamin K Tsang; Takeshi Maruo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  89     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-04     Completed Date:  2004-09-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4069-77     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / metabolism*
Apoptosis / drug effects*
Caspase 3
Caspases / antagonists & inhibitors,  chemistry*
Cells, Cultured
Down-Regulation
Fas Ligand Protein
Female
Humans
Membrane Glycoproteins / metabolism*
Placenta / cytology,  metabolism*
Poly(ADP-ribose) Polymerases / antagonists & inhibitors,  chemistry*
Pregnancy
RNA, Messenger / metabolism
Receptors, Thyroid Hormone / genetics,  metabolism
Triiodothyronine / pharmacology*
Trophoblasts / metabolism*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/RNA, Messenger; 0/Receptors, Thyroid Hormone; 6893-02-3/Triiodothyronine; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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