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.