title: Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin.
abstract: Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control of cell proliferation and stress responses. Our group previously demonstrated induction of the nucleolar protein nucleostemin (NS) in response to cardiac pathological insult. NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective properties. The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event associated with stress response in cardiac cells. Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosomal RNA synthesis occurs in both neonatal rat cardiomyocytes (NRCM) and cardiac progenitor cells (CPC) upon exposure to doxorubicin or actinomycin D. Silencing of NS significantly increases cell death resulting from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death. Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultured cardiomyocytes challenged with doxorubicin. The presence of altered nucleolar structures resulting from myocardial infarction in mice supports the model of nucleolar stress as a general response to pathological injury. Collectively, these findings serve as the initial description of myocardial nucleolar stress and establish the postulate that nucleoli acts as sensors of stress, regulating the cellular response to pathological insults.
authors: San Diego State Heart Institute, San Diego State University, San Diego, CA 92182, USA.
authors: Daniele
authors: D
authors: Avitabile
authors: Brandi
authors: B
authors: Bailey
authors: Christopher T
authors: CT
authors: Cottage
authors: Balaji
authors: B
authors: Sundararaman
authors: Anya
authors: A
authors: Joyo
authors: Michael
authors: M
authors: McGregor
authors: Natalie
authors: N
authors: Gude
authors: Silvia
authors: S
authors: Truffa
authors: Aryan
authors: A
authors: Zarrabi
authors: Mathias
authors: M
authors: Konstandin
authors: Mohsin
authors: M
authors: Khan
authors: Sadia
authors: S
authors: Mohsin
authors: Mirko
authors: M
authors: Völkers
authors: Haruhiro
authors: H
authors: Toko
authors: Matt
authors: M
authors: Mason
authors: Zhaokang
authors: Z
authors: Cheng
authors: Shabana
authors: S
authors: Din
authors: Roberto
authors: R
authors: Alvarez
authors: Kimberlee
authors: K
authors: Fischer
authors: Mark A
authors: MA
authors: Sussman
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000378:metabolism / Q000473:pathology; D019204:GTP-Binding Proteins; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D012335:RNA, Ribosomal / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D051381:Rats; D013312:Stress, Physiological
chemical_list: D002352:Carrier Proteins; C470310:Gnl3 protein, rat; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; C470311:nucleostemin protein, mouse; D000090243:Nucleophosmin; D019204:GTP-Binding Proteins