The involvement of microtubular disruption in methylmercury-induced apoptosis in neuronal and nonneuronal cell lines.
Methylmercury (MeHg) is known to interfere with cell cycle progression by disruption of microtubules. The relationship between the changes in cell cycle and the induction of apoptosis caused by MeHg was investigated in cultured mammalian cells. MeHg caused nuclear fragmentation and DNA ladder formation in rat pheochromocytoma (PC12) and mouse neuroblastoma cells exposed to MeHg. Flow cytometric analysis revealed that the occurrence of apoptosis was preceded by the accumulation of cells in G2/M after MeHg treatment. Exposure to colchicine, a well-characterized mitotic inhibitor, also caused G2/M-phase arrest followed by the appearance of apoptotic cells. These results suggest that G2/M-phase arrest through the disruption of microtubules is an important event in the development of apoptosis by MeHg. MeHg treatment led to G2/M-phase arrest followed by apoptosis in nonneuronal HeLa cells also. Bcl-2 was phosphorylated by MeHg treatment in HeLa cells but not in PC12 cells; however, p53 expression was not changed in either cell line. Thus, MeHg induces apoptosis via a p53-independent pathway in both cell lines, however, different pathways may be activated after the disruption of microtubules in PC12 and HeLa cells.
Miura
K
K
Faculty of Economics, Wako University, 2160, Kanai-cho, Machida-shi, Tokyo, 195-8585, Japan.
Koide
N
N
Himeno
S
S
Nakagawa
I
I
Imura
N
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D003078:Colchicine / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004273:DNA, Neoplasm; D008767:Methylmercury Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D003078:Colchicine