CHARACTERIZATION OF PLATELET-DERIVED GROWTH-FACTOR (PDGF) ACTION ON AMOUSE NEUROBLASTOMA CELL-LINE, NB41, BY INTRODUCTION OF AN ANTISENSE PDGF BETA-RECEPTOR RNA

We have shown previously that platelet-derived growth factor (PDGF) ha s trophic effects on dopaminergic neurons in vitro, We now examined a mouse neuroblastoma cell line, NB41, for its response to PDGF and stud ied their phenotypic characteristics following introduction of an anti sense PDGF beta-receptor RNA, NB41 cells produce both PDGF-AA and -BB; however, they carry only PDGF beta-receptors, responding to BE but no t to AA. Culturing the cells with PDGF-BB induced mRNA for c-fos and P DGF-beta receptor as well as that of neuron-specific enzyme, tyrosine hydroxylase, In contrast, mRNA of chromogranin A, which is produced by chromaffin cells, decreased, Introduction of an antisense PDGF beta-r eceptor RNA in NB41 cells completely suppressed neurite extension and cell growth, We compared the PDGF-beta receptor sense and antisense cl ones for their survival. Following serum withdrawal, NB41 cells showed a DNA ladder, which by an addition of the neurotoxin, 6-hydroxy dopam ine (6-OHDA), resulted in a further enhancement of the DNA ladder, The addition of PDGF-BB prior to 6-OHDA rescued cells from undergoing apo ptosis, seen as a reduction of the DNA ladder. The antisense clone, re gardless of the presence of PDGF-BB in the culture, showed a pronounce d DNA ladder after serum withdrawal, which was further enhanced by the addition of 6-OHDA.