Nerve growth factor effects on pyridine nucleotides after oxidant injury of rat pheochromocytoma cells.
Neurotrophic factors regulate neuronal survival and neurite growth in development and following injury. Oxidative stress produced in neurons as a consequence of primary injury, or during reperfusion following ischemia, may contribute to cell death. Here, the effects of nerve growth factor (NGF) on the response to H2O2 injury were examined in the PC12 rat pheochromocytoma cell line. Specifically, the effect of NGF on cell viability after H2O2 injury was measured. Pretreatment with NGF enhanced survival after H2O2 treatment, as measured by Trypan blue dye exclusion, radiolabeled amino acid incorporation, tetrazolium salt reduction, or cytoplasmic enzyme release. One early event associated with H2O2 treatment was a rapid decrease in NAD+. Although initial decreases in NAD+ levels were similar in control and NGF-treated cells, the latter recovered more rapidly and extensively. The decline in total NAD observed after NGF treatment was almost equal in magnitude to the measured increase in NADP. Inhibition of poly(ADP-ribose) polymerase also enhanced viability following H2O2 injury. Treatment with both NGF and an inhibitor of this enzyme resulted in a greater reduction of H2O2 toxicity than was observed with either agent alone. These data suggest that NGF protection is multifactorial and that a significant component of the NGF effect is due to its regulatory role in the metabolism of pyridine nucleotides.
Jackson
G R
GR
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555.
Werrbach-Perez
K
K
Ezell
E L
EL
Post
J F
JF
Perez-Polo
J R
JR
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D004396:Coloring Agents; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D001549:Benzamides; D004396:Coloring Agents; D009414:Nerve Growth Factors; D013778:Tetrazolium Salts; D013844:Thiazoles; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D009249:NADP; C025160:3-aminobenzamide; D006861:Hydrogen Peroxide; C022616:thiazolyl blue