title: NPR-C protects embryonic stem cells from apoptosis by regulating p53 levels.
abstract: The identification of intrinsic factors required for propagation of self-renewing embryonic stem (ES) cells is important to improve the efficiency of expansion of ES cells for therapeutic purposes. Here, we report a novel role for natriuretic peptide receptor-C (NPR-C) in the survival of murine ES cells. We found that NPR-C was highly expressed in ES cells and was downregulated during ES cell differentiation. Knockdown of NPR-C in ES cells by using a small-interfering RNA resulted in apoptotic cell death, and the induction of p53 protein expression. Conversely, chemical inhibition of p53 by α-pifithrin significantly reduced apoptosis in NPR-C-deficient cells. cANF((4-23)), a selective NPR-C agonist, protected ES cells against oxidative stress-induced apoptosis, and blocked activation of p53 and Nanog suppression in the presence of DNA-damaging agents. Thus, NPR-C is required to control DNA damage-induced p53 levels to maintain ES cell self-renewal.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Japan. essam_abdelalim@yahoo.com
authors.forename: Essam M
authors.initials: EM
authors.lastname: Abdelalim
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C