Nurr1 and PPAR gamma protect PC12 cells against MPP super(+) toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment

• Published in: Molecular and cellular biochemistry 2016-09, Vol.420 (1-2), p.29-42
• Main Authors: Jodeiri Farshbaf, Mohammad, ouzanfar, Mahboobeh, Ghaedi, Kamran, Kiani-Esfahani, Abbas, Peymani, Maryam, Shoaraye Nejati, Alireza, Izadi, Tayebeh, Karbalaie, Khadijeh, Noorbakhshnia, Maryam, Rahgozar, Soheila, Baharvand, Hossein, Nasr-Esfahani, Mohammad Hossein
• Format: Article
• Language: English
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-016-2764-4

Parkinson's disease (PD) can degenerate dopaminergic (DA) neurons in midbrain, substantia-nigra pars compacta. Alleviation of its symptoms and protection of normal neurons against degeneration are the main aspects of researches to establish novel therapeutic strategies. PPAR gamma as a member of PPARs have shown neuroprotection in a number of neurodegenerative disorders such as Alzheimer's disease and PD. Nuclear receptor related 1 protein (Nurr1) is, respectively, member of NR4A family and has received great attentions as potential target for development, maintenance, and survival of DA neurons. Based on neuroprotective effects of PPAR gamma and dual role of Nurr1 in anti-inflammatory pathways and development of DA neurons, we hypothesize that PPAR gamma and Nurr1 agonists alone and in combined form can be targets for neuroprotective therapeutic development for PD in vitro model. 1-Methyl-4-phenylpyridinium (MPP super(+)) induced neurotoxicity in PC12 cells as an in vitro model for PD studies. Treatment/cotreatment with PPAR gamma and Nurr1 agonists 24 h prior to MPP super(+) induction enhanced the viability of PC12 cell. The viability of PC12 cells was determined by MTS test. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were detected by flow cytometry. In addition, the relative expression of four genes including TH (the marker of DA neurons), Ephrin A1, Nurr1, and Ferritin light chain were assessed by RT-qPCR. In the MPP super(+)-pretreated PC12 cells, PPAR gamma and Nurr1 agonists and their combined form resulted in a decrease in the cell death rate. Moreover, production of intracellular ROS and MMP modulated by MPP super(+) was decreased by PPAR gamma and Nurr1 agonists' treatment alone and in the combined form.