Document Detail


Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin.
MedLine Citation:
PMID:  12506112     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular defects in apoptotic pathways are thought to often contribute to the abnormal expansion of malignant cells and their resistance to chemotherapy. Therefore, a comprehensive knowledge of the mechanisms controlling induction of apoptosis and subsequent cellular disintegration could result in improved methods for prognosis and treatment of cancer. In this study, we have examined apoptosis-induced alterations in two proteins, nucleolin and poly(ADP-ribose) polymerase-1 (PARP-1), in U937 leukemia cells. Nucleolin is expressed at high levels in malignant cells, and it is a multifunctional and mobile protein that can shuttle among the nucleolus, nucleoplasm, cytoplasm, and plasma membrane. Here, we report our findings that UV irradiation or camptothecin treatment of U937 cells induced apoptosis and caused a significant change in the levels and localization of nucleolin within the nucleus. Additionally, nucleolin levels were dramatically decreased in extracts containing the cytoplasm and plasma membrane. These alterations could be abrogated by pre-incubation with an inhibitor of PARP-1 (3-aminobenzamide), and our data support a potential role for nucleolin in removing cleaved PARP-1 from dying cells. Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies. These results indicate that nucleolin plays an important role in apoptosis, and could be a useful marker for assessing apoptosis or detecting apoptotic bodies. In addition, the data provide a possible explanation for the appearance of nucleolin and PARP-1 autoantibodies in some autoimmune diseases.
Authors:
Yingchang Mi; Shelia D Thomas; Xiaohua Xu; Lavona K Casson; Donald M Miller; Paula J Bates
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2002-12-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-03     Completed Date:  2003-04-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8572-9     Citation Subset:  IM    
Affiliation:
Molecular Targets Group, James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Kentucky 40202, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis* / radiation effects
Benzamides / pharmacology
Camptothecin / pharmacology
Enzyme Inhibitors / pharmacology
Humans
In Situ Nick-End Labeling
Leukemia, Myeloid / enzymology,  metabolism,  pathology*
Phosphoproteins / metabolism*
Poly(ADP-ribose) Polymerases / antagonists & inhibitors,  metabolism
Precipitin Tests
RNA-Binding Proteins / metabolism*
U937 Cells
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/Benzamides; 0/Enzyme Inhibitors; 0/Phosphoproteins; 0/RNA-Binding Proteins; 0/nucleolin; 3544-24-9/3-aminobenzamide; 7689-03-4/Camptothecin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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