Manganese (Mn)-induced neurotoxicity has aroused public concerns for many years, but its precise mechanism is still poorly understood. Herein, we report the impacts of the
phosphatidylinositol 3-kinase/
protein kinase B (PI3K/Akt) signaling pathway in mediating neurological effects induced by
manganese sulfate (MnSO4) exposure in PC12 cells. In this study, cells were treated with MnSO4 for 24 h in the absence or presence of
LY294002 (a special inhibitor of PI3K). We investigated cell viability and apoptosis signals, as well as levels of
superoxide dismutase (SOD),
glutathione peroxidase (GSH-Px),
catalase (CAT), and
malondialdehyde (MDA). The
mRNA levels of
B-cell lymphoma 2 (Bcl-2),
Bcl-2-associated X protein (Bax), and
Caspase-3 were also quantified through real-time quantitative PCR (RT-qPCR);
protein levels of
serine/threonine protein kinase (Akt) and forkhead box O3A (Foxo3a) were determined by western blot. Increasing of MnSO4 doses led to decreased SOD, GSH-Px, and CAT activities, while the level of MDA was upregulated. Moreover, cell apoptosis was significantly increased, as the
mRNA of Bcl-2 and
Caspase-3 was significantly decreased, while Bax
mRNA was increased. Phosphorylated Akt (p-Akt) and Foxo3a (p-Foxo3a) were upregulated in a dose-dependent manner. In addition,
LY294002 pretreatment reduced the activity of SOD, GSH-Px, and CAT but elevated MDA levels. Meanwhile,
LY294002 pretreatment also increased cell apoptosis given the upregulated Bax and
Caspase-3 mRNAs and decreased Bcl-2
mRNA. In summary, the PI3K/Akt signaling pathway can be activated by MnSO4 exposure and mediate MnSO4-induced neurotoxicity.