Regulation of chromogranin biosynthesis by neurotrophic growth factors in neuroblastoma cells

Polypeptide growth factors secreted from the target tissue determine the ch oice of transmitter synthesis in the innervating nerves. We have investigat ed whether they also influence the expression of chromogranins and neuropep tide Y, components co-stored with the neurotransmitters within large dense- core vesicles. IMR-32 and SH-SY5Y human neuroblastoma cells were treated fo r up to six days with various neurotrophic growth and differentiation facto rs. For chromogranins A and B, no significant changes at the mRNA level wer e observed and for chromogranin A this was confirmed at the protein level. The expression of secretogranin II/pro-secretoneurin mRNA, however, was con siderably enhanced in both cell lines after basic fibroblast growth factor treatment. In IMR-32 cells we determined a fast and continuous induction, w hereas the up-regulation in SH-SY5Y cells was more delayed. A transient ele vation of secretogranin II/pro-secretoneurin mRNA levels was seen in SH-SY5 Y cells in response to epidermal growth factor. In these cells we also meas ured the amounts of secretogranin II/prosecretoneurin protein which were in creased by both growth factors. In addition to the above described changes in secretogranin II/pro-secretoneurin biosynthesis we extended and confirme d data available on neuropeptide Y. We found a qualitatively similar patter n of biosynthesis regulation as for secretogranin II/pro-secretoneurin, ind icating that the ultimately increased expression of the two proteins may be characteristic of the phenotypic differentiation after growth factor treat ment. Moreover, this finding of a concomitant regulation further emphasizes the concept of secretogranin II/pro-secretoneurin being a neuropeptide pre cursor from which the functional peptide secretoneurin is proteolytically l iberated. (C) 2000 Elsevier Science Ltd. All rights reserved.