Document Detail


Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin.
MedLine Citation:
PMID:  21444791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Daniele Avitabile; Brandi Bailey; Christopher T Cottage; Balaji Sundararaman; Anya Joyo; Michael McGregor; Natalie Gude; Silvia Truffa; Aryan Zarrabi; Mathias Konstandin; Mohsin Khan; Sadia Mohsin; Mirko Völkers; Haruhiro Toko; Matt Mason; Zhaokang Cheng; Shabana Din; Roberto Alvarez; Kimberlee Fischer; Mark A Sussman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-06-27     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6145-50     Citation Subset:  IM    
Affiliation:
San Diego State Heart Institute, San Diego State University, San Diego, CA 92182, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / metabolism,  pathology
Apoptosis
Carrier Proteins / metabolism*
Cell Nucleolus / metabolism*,  pathology
Cells, Cultured
Constriction, Pathologic / metabolism,  pathology
Humans
Mice
Myocardial Infarction / metabolism,  pathology
Myocardium / metabolism*,  pathology
Myocytes, Cardiac / metabolism,  pathology
Nuclear Proteins / metabolism*
RNA, Ribosomal / biosynthesis
Rats
Stress, Physiological*
Grant Support
ID/Acronym/Agency:
1 R21 HL104544-01/HL/NHLBI NIH HHS; 1R21HL102714-01/HL/NHLBI NIH HHS; 2 R01 HL067245/HL/NHLBI NIH HHS; IR37 HL091102-01/HL/NHLBI NIH HHS; P01HL085577-05/HL/NHLBI NIH HHS; R21 HL102613-01/HL/NHLBI NIH HHS; RC1HL100891-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Nuclear Proteins; 0/RNA, Ribosomal; 0/nucleostemin protein, mouse; 0/nucleostemin protein, rat; 117896-08-9/nucleophosmin
Comments/Corrections

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