[Cytopathological effects of protein synthesis inhibitor emetine on HeLa cells and their nucleoli].
Eukaryotic cell nucleolus is a highly dynamic structure, which is sensitive to all changes within or outside cell borders. Numerous data are available on changes of the nucleolar structure and functions under different treatments. However, almost nothing is known about the action of translation inhibitors on the nucleolus, although these substances, together with TNF-alpha, are commonly used for apoptosis induction, both for scientific and therapeutic purposes. Emetine is one of such inhibitors. We have shown that emetine suppresses cell viability, decreases mitotic index, and induces apoptosis in HeLa cells. Emetine action is irreversible, and it sensitizes cells to unfavourable external conditions. The emetine action causes redistribution of UBF, one of RNA-polymerase I factor, from the nucleolus to nucleoplasm even after a short exposure, i.e. when the morphology of the nucleus and chromatin still keeps its native pattern. It is important that other nucleolar proteins, such as fibrillarin and B23, are not recognized in the nucleoplasm until the very late stages of apoptotic process. A suggestion is made that changes in UBF localization may be associated with the onset of ribosomal repeat cleavage and migration of rDNA-"free" fragments from the nucleolus to nucleoplasm. It looks likely that these changes can serve as an initial morphological indication of apoptosis.
Smirnova
O Iu
OIu
A. N. Belozersky Institute of Physical and Chemical Biology, Moscow State University.
Mishina
V A
VA
Zatsepina
O V
OV
D017209:Apoptosis; D002466:Cell Nucleolus / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004640:Emetine / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D008940:Mitotic Index; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012318:RNA Polymerase I / Q000378:metabolism
D035463:Pol1 Transcription Initiation Complex Proteins; D011500:Protein Synthesis Inhibitors; C063844:transcription factor UBF; D012318:RNA Polymerase I; D004640:Emetine