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Mol Cell Biochem. 2016 Sep;420(1-2):29-42. doi: 10.1007/s11010-016-2764-4. Epub 2016 Jul 19.

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

Author information

1
Department of Biology, School of Sciences, University of Isfahan, Isfahan, 81746-73441, Iran.
2
Department of Biology, New Mexico State University, Las Cruces, NM, USA.
3
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 81593-58686, Iran.
4
Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
5
Department of Biology, School of Sciences, University of Isfahan, Isfahan, 81746-73441, Iran. kamranghaedi@royaninstitute.org.
6
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 81593-58686, Iran. kamranghaedi@royaninstitute.org.
7
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 19395-4644, Iran. Baharvand@royaninstitute.org.
8
Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran. Baharvand@royaninstitute.org.
9
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 81593-58686, Iran. mh_nasr@royaninstitute.org.

Abstract

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. PPARγ 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 PPARγ and dual role of Nurr1 in anti-inflammatory pathways and development of DA neurons, we hypothesize that PPARγ 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(+)) induced neurotoxicity in PC12 cells as an in vitro model for PD studies. Treatment/cotreatment with PPARγ and Nurr1 agonists 24 h prior to MPP(+) 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(+)-pretreated PC12 cells, PPARγ 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(+) was decreased by PPARγ and Nurr1 agonists' treatment alone and in the combined form.

KEYWORDS:

MPP+; Nurr1; PC12; PPARγ; Parkinson’s disease

PMID:
27435855
DOI:
10.1007/s11010-016-2764-4
[Indexed for MEDLINE]

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