Molecular mechanism of apoptosis and gene expressions in human lymphoma U937 cells treated with anisomycin.
Anisomycin is known as a potent apoptosis inducer by activating JNK/SAPK and inhibiting protein synthesis during translation. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by anisomycin using DNA microarrays and computational gene-expression analysis tools in human lymphoma U937 cells. Anisomycin was found to induce apoptosis in time- and concentration-dependent manner as confirmed by phosphatidylserine externalization and DNA fragmentation analysis. Furthermore, anisomycin-treated cells also showed caspase-8 activation, mitochondrial membrane potential collapse, Bid activation, caspase-3 cleavage and cytochrome c release into the cytosol. In the gene-expression analysis, six gene clusters were detected. From clusters I and II, three significant genetic networks were identified. Interestingly, many bZIP family transcription factors were observed in the up-regulated genetic networks. Moreover, the expression of protein-synthesis-related genes, such as EIF4 family proteins and ribosomal proteins, were inhibited. This finding could explain the reason why anisomycin inhibits the protein synthesis at the translation steps. These results provide novel information for understanding the molecular mechanism of apoptosis induced by anisomycin.
Hori
Takeshi
T
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama 930-0194, Japan.
Kondo
Takashi
T
Tabuchi
Yoshiaki
Y
Takasaki
Ichiro
I
Zhao
Qing-Li
QL
Kanamori
Masahiko
M
Yasuda
Taketoshi
T
Kimura
Tomoatsu
T
D000841:Anisomycin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020298:U937 Cells
D017931:DNA Primers; D000841:Anisomycin