Neurotrophin-3 reduces apoptosis induced by 6-OHDA in PC12 cells through Akt signaling pathway.
Previous work has demonstrated that 6-hydroxydopamine (6-OHDA) induces apoptosis in PC12 cells. The goal of the present study was to investigate the mechanisms underlying the protection by neurotrophin-3 (NT-3) against 6-OHDA-induced apoptosis in PC12 cells. Treatment of PC12 cells with 6-OHDA resulted in activation of caspase-3 and subsequent apoptosis, as detected by TUNEL staining. In addition, Akt phosphorylation was decreased following 6-OHDA treatment. Pretreatment with NT-3 reduced the percentage of apoptotic cells and caspase-3 activity induced by 6-OHDA and suppressed the cleavage of caspase-3 and Poly(ADP-ribose) polymerase (PARP) with a significant decrease in cell viability. Moreover, Akt phosphorylation was enhanced and 6-OHDA-induced chromatin condensation was suppressed by NT-3. Such NT-3-evoked suppression in chromatin condensation was reversed by anti-TrkA antibody receptor blockade. Further study revealed that LY294002, an inhibitor of PI3-kinase (a molecule upstream of Akt), enhanced 6-OHDA-induced apoptosis. These data indicate that NT-3 prevents 6-OHDA-induced apoptosis in PC12 cells via activation of PI3-kinase/Akt pathway.
Li
Zhiquan
Z
PLA Institute of Othropadics & Traumatology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Hu
Yunyu
Y
Zhu
Qingsheng
Q
Zhu
Jinyu
J
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D009025:Morpholines / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D018663:Adrenergic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D020933:Neurotrophin 3; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016627:Oxidopamine; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3