Journal article
Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin
Proceedings of the National Academy of Sciences - PNAS, Vol.108(15), pp.6145-6150
04/12/2011
Handle:
https://hdl.handle.net/2376/108451
PMCID: PMC3076816
PMID: 21444791
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.
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Details
- Title
- Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin
- Creators
- Daniele Avitabile - San Diego State Heart Institute, San Diego State University, San Diego, CA 92182, USABrandi BaileyChristopher T CottageBalaji SundararamanAnya JoyoMichael McGregorNatalie GudeSilvia TruffaAryan ZarrabiMathias KonstandinMohsin KhanSadia MohsinMirko VölkersHaruhiro TokoMatt MasonZhaokang ChengShabana DinRoberto Alvarez, JrKimberlee FischerMark A Sussman
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(15), pp.6145-6150
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- United States
- Grant note
- 1 R21 HL104544-01 / NHLBI NIH HHS IR37 HL091102-01 / NHLBI NIH HHS RC1 HL100891 / NHLBI NIH HHS 2 R01 HL067245 / NHLBI NIH HHS P01 HL085577 / NHLBI NIH HHS 1R21HL102714-01 / NHLBI NIH HHS R37 HL091102 / NHLBI NIH HHS R21 HL102613-01 / NHLBI NIH HHS R21 HL102613 / NHLBI NIH HHS R01 HL067245 / NHLBI NIH HHS R21 HL102714 / NHLBI NIH HHS P01HL085577-05 / NHLBI NIH HHS R21 HL104544 / NHLBI NIH HHS RC1HL100891-02 / NHLBI NIH HHS
- Identifiers
- 99900547191601842
- Language
- English
- Resource Type
- Journal article