Nerve growth factor induces sensitivity to botulinum neurotoxin type A in norepinephrine-secreting PC12 cells.
Inhibition of Ca(2+)-activated norepinephrine secretion by the botulinum neurotoxin (NT) serotypes A and E was examined in permeabilized PC12 cells. The dichain type E NT reduced with dithiothreitol (DTT) completely inhibited secretion whereas the dichain type A NT reduced with DTT exhibited incomplete inhibitory activity. In contrast, Ca(2+)-activated secretion in PC12 cells treated with nerve growth factor (NGF) was completely inhibited by reduced type A NT. The NGF-treated PC12 cells retained a sensitivity to the type E NT similar to that of untreated PC12 cells. These results indicate that the intracellular mechanisms of inhibition of the types E and A NTs are distinct. NGF appears to either induce the expression of a component selectively required for type A NT sensitivity, or otherwise modifies the secretory apparatus to acquire type A NT sensitivity.
Banerjee
A
A
Department of Food Microbiology and Toxicology, University of Wisconsin, Madison 53706.
Martin
T F
TF
DasGupta
B R
BR
D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity*; D002118:Calcium / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004229:Dithiothreitol / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D009414:Nerve Growth Factors; D009498:Neurotoxins; D001905:Botulinum Toxins; D011188:Potassium; D002118:Calcium; D004229:Dithiothreitol; D009638:Norepinephrine