Neurochemical Research

, Volume 44, Issue 9, pp 2103–2112 | Cite as

Apelin-13 Protects PC12 Cells Against Methamphetamine-Induced Oxidative Stress, Autophagy and Apoptosis

  • Kobra Foroughi
  • Mehdi Khaksari
  • Majid Rahmati
  • Fateme Sadat Bitaraf
  • Asghar ShayanniaEmail author
Original Paper


Methamphetamine (METH) is a potent psychomotor stimulant that has a high potential for abuse in humans. In addition, it is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to METH causes psychosis and increases the risk of Parkinson’s disease. Apelin-13 is a novel endogenous ligand which studies have shown that may have a neuroprotective effect. Therefore, we hypothesized that Apelin-13 might adequately prevent METH-induced neurotoxicity via the inhibition of apoptotic, autophagy, and ROS responses. In this study, PC12 cells were exposed to both METH (0.5, 1, 2, 3, 4, 6 mmol/L) and Apelin-13 (0.5, 1.0, 2.0, 4.0, 8.0 μmol/L) in vitro for 24 h to measure determined dose, and then downstream pathways were measured to investigate apoptosis, autophagy, and ROS responses. The results have indicated that Apelin-13 decreased the apoptotic response post-METH exposure in PC12 cells by increasing cell viability, reducing apoptotic rates. In addition, the study has revealed Apelin-13 decreased gene expression of Beclin-1 by Real-Time PCR and LC3-II by western blotting in METH-induced PC12 cells, which demonstrated autophagy is reduced. In addition, this study has shown that Apelin-13 reduces intracellular ROS of METH-induced PC12 cells. These results support Apelin-13 to be investigated as a potential drug for treatment of neurodegenerative diseases. It is suggested that Apelin-13 is beneficial in reducing oxidative stress, which may also play an important role in the regulation of METH-triggered apoptotic response. Hence, these data indicate that Apelin-13 could potentially alleviate METH-induced neurotoxicity via the reduction of oxidative damages, apoptotic, and autophagy cell death.


Methamphetamine Apelin-13 Neurotoxicity Apoptosis Autophagy Reactive oxygen species 



The present study was supported by Shahroud University of medical sciences as an MSc Thesis. We hereby acknowledge the research deputy for grant No 9667.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interests related to this work.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Research Involving Human and Animal Participants

This article does not contain any studies with human participants performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kobra Foroughi
    • 1
  • Mehdi Khaksari
    • 2
  • Majid Rahmati
    • 3
  • Fateme Sadat Bitaraf
    • 4
  • Asghar Shayannia
    • 5
    Email author
  1. 1.Student Research Committee, School of MedicineShahroud University of Medical SciencesShahroudIran
  2. 2.Addiction Research CenterShahroud University of Medical SciencesShahroudIran
  3. 3.Cancer Prevention Research CenterShahroud University of Medical SciencesShahroudIran
  4. 4.Department of Medical Biotechnology, School of MedicineShahroud University of Medical SciencesShahroudIran
  5. 5.Bahar Center for Education, Research and TreatmentShahroud University of Medical SciencesShahroudIran

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