Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent.

Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Research Abstract Details 

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Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Abstract Text:

Hirofumi Yamauchi,Kei-ichi Katayama,Masaki Ueno,Xi Jun He,Takashi Mikami,Koji Uetsuka,Kunio Doi,Hiroyuki Nakayama,Hirofumi Yamauchi,Kei-ichi Katayama,Masaki Ueno,Xi Jun He,Takashi Mikami,Koji Uetsuka,Kunio Doi,Hiroyuki Nakayama,

Placental apoptosis plays important roles in both normal morphogenesis and pathogenesis. We previously reported that administration of cytosine arabinoside (Ara-C), a DNA-damaging agent, to pregnant rats induced apoptosis of trophoblasts in the placental labyrinth zone. Our aim here was to clarify the molecular pathway of DNA damage induced-trophoblastic apoptosis. We found the accumulation and phosphorylation of p53 protein, a tumor suppressor that mediates apoptosis under various cellular stresses, in Ara-C-treated rat placentas. Expression of the mRNAs of downstream targets of p53 was upregulated, suggesting that p53 exerts its function as a transcription factor. We also observed release of mitochondrial cytochrome c and activation of caspase-9, hallmarks of the intrinsic apoptotic pathway. Phosphorylation of Chk1 and H2A.X, target substrates of DNA damage transducers, was detected immediately after Ara-C treatment, suggesting activation of DNA damage cascades to phosphorylate p53. Ara-C-induced trophoblastic apoptosis was almost completely abrogated in placentas of Trp53 (coding p53)-deficient mice, whereas the levels of physiological apoptosis in trophoblasts were similar among wild-type and Trp53-deficient mice. These results indicate that p53 is essential for DNA damage-induced trophoblastic apoptosis and suggest that the mechanisms that regulate the damage-induced apoptosis differ from those that regulate physiological apoptosis.

Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Publishing Authors By Initials

H Yamauchi,K Katayama,M Ueno,XJ He,T Mikami,K Uetsuka,K Doi,H Nakayama,H Yamauchi,K Katayama,M Ueno,XJ He,T Mikami,K Uetsuka,K Doi,H Nakayama,

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Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Apoptosis : an international journal on programmed

VOLUME: 12

Page Numbers: 1743-54

Journal Abbreviation: Apoptosis

ISSN: 1360-8185

DAY: 1

MONTH: Oct

YEAR: 2007

Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent. Information

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LANGUAGE: eng

NlmUniqueID: 9712129

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Grant and Affiliation Information for Essential role of p53 in trophoblastic apoptosis induced in the developing rodent placenta by treatment with a DNA-damaging agent.

AFFILIATION: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan. yamauchi-h@umin.net

Country: United States

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MEDLINETA: Apoptosis

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