MODULATION OF P36 GENE-EXPRESSION IN HUMAN NEURONAL CELLS

p36 is a calcium/lipid-binding phosphoprotein that is expressed at hig h levels in proliferating and transformed cells, and at low levels in terminally differentiated cells, such as CNS neurons. The calcium-depe ndent binding to membrane phospholipids, and its capacity to interact with intermediate filament proteins suggest that p36 may be involved i n the transduction of extracellular signals. The present work examines p36 gene expression in the mature CNS, primary primitive neuroectoder mal tumors (PNETs), and transformed PNET cell lines. p36 immunoreactiv ity was not observed in normal adult human brain, but low levels of th e protein were detected by Western blot analysis. Following acute anox ic cerebral injury, the mean levels of p36 protein were elevated two-f old, and injured neurons exhibited increased p36 immunoreactivity. Thi s phenomenon was likely to have been mediated by post-transcriptional mechanisms since there was no corresponding change in the level p36 mR NA. p36 immunoreactivity was detected in 8 of 9 primary PNETs, and in 3 of 3 neurofilament-expressing PNET cell lines. The levels of p36 pro tein in PNET cell lines were 5-fold higher than in adult human brain t issue. Although p36 gene expression was generally high in proliferatin g PNET cells, the levels of p36 mRNA and protein were not strictly cor related with DNA synthesis. Instead, p36 gene expression was modulated in both proliferating and non-proliferating PNET cell cultures by tre atment with 50 mIU/ml of insulin, 100 mM ethanol, or 5 mu M retinoic a cid. The frequent discordances observed experimentally and in vivo bet ween p36 mRNA and p36 protein expression suggest that the steady-state levels of p36 protein in neuronal cells may be regulated primarily by post-transcriptional mechanisms.