Expression of a splice variant of prion protein during hypoxia in human glioblastoma cell line T98G
2005
Human prion diseases occur in sporadic, genetic, and transmitted forms. It is associated with the conversion of normal cellular prion protein (PrPC) into a protease-resistant isoform (PrPres). We have shown previously that the human glioblastoma cell line T98G had no coding-region mutation of the prion protein gene (PRNP) which was of the 129 M/V genotype and produced a form of proteinase K-resistant prion protein (PrP) fragment following long-term culture and high passage number (Kikuchi et. al., 2004, J. Gen. Virol. 85, 3449–3457). In this study, we identified an unusual alternative splicing occurring within the exon 2, which resulted in the generation of mRNA laking a C-terminal glycosylphosphatidylinositol (GPI) anchor signal sequence. Only a low level of an alternative spliced form of PRNP was identified in T98G cells under normoxia. Under hypoxia, however, expression levels of the alternatively spliced mRNA were increased. Treatment with cobalt chloride, which mimics anoxia, also increased its expression levels in T98G cells. These results indicate that decrease in oxygen pressure may modulate the PRNP gene expression. The alternatively spliced mRNA encoded the 231 amino acids of polypeptide, which consisted of the amino-terminal portion of PrP and additional residues at its carboxy terminus.
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