Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells.
Acidic (aFGF) and basic (bFGF) fibroblast growth factors are well-characterized peptide hormones that have potent angiogenic activity and that are mitogenic for a variety of cell types. The present findings demonstrate that FGFs can reproduce the entire spectrum of rat pheochromocytoma PC12 cell responses previously shown to be elicited by NGF. These include responses that are rapid (cell flattening, enhanced phosphorylation of tyrosine hydroxylase) or delayed (neurite outgrowth, induction of phosphorylated MAP 1.2, regulation of NILE and Thy-1 glycoproteins, cessation of mitosis, elevation of AChE activity), as well as responses that have been shown to be either transcription-independent (neurite regeneration, promotion of survival) or transcription-dependent (priming, regulation of NILE and Thy-1 glycoproteins, elevation of AChE activity). The only responses for which the FGFs and NGF consistently showed quantitative differences were in the rates for neurite initiation and elongation in serum-containing medium. Thus, while all 3 factors promoted the formation of stable neurites, the network of outgrowth elicited by NGF at any given time of treatment was always of greater density. Togari et al. (1985) have previously reported that bFGF can initiate transient neurite formation in PC12 cell cultures. The present observations describe a variety of additional actions of bFGF on a neuronal cell line, and demonstrate that aFGF is capable of mimicking many, if not all, of these actions. These observations thus extend the range of actions that aFGF and bFGF may potentially exert on nerve cells, either during their development, repair, or maintenance. In addition, this work suggests that the PC12 cell line may serve as a useful model system with which to study the mechanism of action of FGFs on neurons. Since all 3 factors appear capable of eliciting the same wide spectrum of responses, molecular events specifically associated with FGFs and NGF in PC12 cells may prove illuminating of the causal steps involved in neuronal differentiation.
Rydel
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Department of Pharmacology, New York University School of Medicine, New York 10016.
Greene
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D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D008858:Microscopy, Phase-Contrast; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D051381:Rats; D012038:Regeneration; D014158:Transcription, Genetic
D009414:Nerve Growth Factors; D011506:Proteins; D005346:Fibroblast Growth Factors; D000110:Acetylcholinesterase