Nucleolar stress is an early response to myocardial damage involving nucleolar proteins nucleostemin and nucleophosmin

被引：71

作者：

Avitabile, Daniele ^{[1
]}

Bailey, Brandi ^{[1
]}

Cottage, Christopher T. ^{[1
]}

Sundararaman, Balaji ^{[1
]}

Joyo, Anya ^{[1
]}

McGregor, Michael ^{[1
]}

Gude, Natalie ^{[1
]}

Truffa, Silvia ^{[1
]}

Zarrabi, Aryan ^{[1
]}

Konstandin, Mathias ^{[1
]}

Khan, Mohsin ^{[1
]}

Mohsin, Sadia ^{[1
]}

Voelkers, Mirko ^{[1
]}

Toko, Haruhiro ^{[1
]}

Mason, Matt ^{[1
]}

Cheng, Zhaokang ^{[1
]}

Din, Shabana ^{[1
]}

Alvarez, Roberto, Jr. ^{[1
]}

Fischer, Kimberlee ^{[1
]}

Sussman, Mark A. ^{[1
]}

机构：

[1] San Diego State Univ, San Diego State Heart Inst, San Diego, CA 92182 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 15期

基金：

美国国家卫生研究院;

关键词：

nucleolus; rRNA; hypoxia; hypertrophy; CELL-CYCLE ARREST; RIBOSOMAL-RNA SYNTHESIS; FACTOR TIF-IA; STEM/PROGENITOR CELLS; INDUCED APOPTOSIS; NUCLEAR EXPORT; CANCER-CELLS; STEM-CELLS; P53; TRANSCRIPTION;

D O I：

10.1073/pnas.1017935108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：6145 / 6150

页数：6

共 42 条

[1] Depletion of nucleophosmin leads to distortion of nucleolar and nuclear structures in HeLa cells [J].