Nerve growth factor prevents the apoptosis-associated increase in acetylcholinesterase activity after hydrogen peroxide treatment by activating Akt.
Acetylcholinesterase (AChE) is thought to play an important role during apoptosis. Our results showed that H2O2 induced AChE activity, a functional marker in apoptosis, increases in neuronal-like PC12 cells. Glutathione, which is involved in cellular redox homeostasis, inhibited the increase of AChE activity, suggesting that reactive oxygen species (ROS) play a key role in this process. Further investigation showed that the elevation of AChE was observed after the degradation of Akt, release of cytochrome c from mitochondria into the cytosol, and activation of caspase family members. When nerve growth factor (NGF) was present, with the maintenance of Akt level, the elevation of AChE, the cytochrome c diffusion, as well as apoptosis were markedly attenuated in H2O2-treated PC12 cells. However, wortmannin, an inhibitor of the PI3K/Akt pathway, accelerated the apoptosis and increased the AChE activity. The overexpression of constitutively activated Akt, which is a downstream signalling element of the NGF receptor TrkA, delayed mitochondrial collapse and inhibited elevation of AChE activity. Thus, NGF prevented apoptosis and elevation of AChE activity by activating the Akt pathway and stabilizing the function of mitochondria.
Jiang
Hua
H
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Jingya
J
Zhu
Hui
H
Li
Hong
H
Zhang
Xuejun
X
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
D045304:Cytochromes c; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D000110:Acetylcholinesterase; D053148:Caspase 3; D005978:Glutathione