Enhancement of Peroxynitrite-Induced Apoptosis in PC12 Cells by Fibroblast Growth Factor-1 and Nerve Growth Factor Requires p21Ras Activation and Is Suppressed by Bcl-2

1998 ◽  
Vol 356 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Nathan Spear ◽  
Alvaro G. Estévez ◽  
Gail V.W. Johnson ◽  
Dale E. Bredesen ◽  
John A. Thompson ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pc12 Cells ◽  
Fibroblast Growth ◽  
Nerve Growth ◽  
Induced Apoptosis

scholarly journals Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate.

1993 ◽  
Vol 121 (2) ◽  
pp. 409-422 ◽  
Author(s):  
Y Y Wu ◽  
R A Bradshaw
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pc12 Cells ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Phosphatases ◽  
Secondary Response ◽  
Fibroblast Growth ◽  
Tyrosine Phosphatases ◽  
Nerve Growth

Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases.

scholarly journals Carbachol stimulates a different phospholipid metabolism than nerve growth factor and basic fibroblast growth factor in PC12 cells.

1991 ◽  
Vol 2 (5) ◽  
pp. 383-390 ◽  
Author(s):  
M S Pessin ◽  
J G Altin ◽  
M Jarpe ◽  
F Tansley ◽  
R A Bradshaw ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pc12 Cells ◽  
Basic Fibroblast Growth Factor ◽  
Molecular Species ◽  
Muscarinic Agonist ◽  
Fibroblast Growth ◽  
Nerve Growth ◽  
Phosphatidylcholine Hydrolysis

We have examined 1,2-diglycerides (DGs) generated in PC12 cells in response to the muscarinic agonist carbachol and compared them with those generated in response to the differentiation factors nerve growth factor and basic fibroblast growth factor. Whereas carbachol stimulates a greater release of inositol phosphates, all three agonists generate similar levels of DGs. In this report, we have analyzed the molecular species of PC12 DGs generated in response to these three agonists. Additionally, we have analyzed the molecular species of PC12 phospholipids. The data indicate that 1) after 1 min of either nerve growth factor or basic fibroblast growth factor stimulation, DGs arise primarily from phosphoinositide hydrolysis; 2) in contrast, after 1 min of carbachol stimulation, DG are generated equally by both phosphoinositide and phosphatidylcholine hydrolysis; and 3) after 15 min of stimulation by any of these agonists, DGs are generated largely by phosphatidylcholine hydrolysis, with a smaller component arising from the phosphoinositides. These results suggest that at least part of the mechanism by which PC12 cells distinguish between different agonists is via alterations in phospholipid sources and kinetics of DG generation.

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