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Abstract
Methamphetamine (METH) is an illicit dopaminergic neurotoxin and is an extremely addictive psychostimulant drug that influences monoamine neurotransmitter system of the brain and is responsible for enhancing energy and satisfaction and feelings of alertness. Long-lasting exposure to METH causes psychosis and increases the risk of Parkinson’s disease. Studies have revealed that obestatin (OB) is a novel endogenous ligand, which may have neuroprotective effects. Hence, we hypothesized that OB might appropriately limit METH-induced neurotoxicity via the control of apoptotis and autophagy. In the current study, PC12 cells were exposed to both METH (0.5, 1, 2, 3, 4, and 6 mmol/L) and pretreatment OB (1, 10, 100, and 200 nmol/L) in vitro for 24 h to determine appropriate dose, and then downstream pathways were measured to investigate apoptosis and autophagy. The results have shown that OB reduced the apoptotic response post-METH exposure in PC12 cells by developing cell viability and diminishing apoptotic rates. Furthermore, the study has exhibited OB decreased gene expression of Beclin-1 by real-time polymerase chain reaction and LC3-II by Western blotting in METH-induced PC12 cells, which demonstrated that autophagy is reduced. The study is proposed that OB is useful in reducing oxidative stress, which may also play an essential role in the regulation of METH-triggered apoptotic response. So these data indicate that OB could potentially alleviate METH-induced neurotoxicity via the reduction of apoptotic and autophagy responses.
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