Uric acid demonstrates neuroprotective effect on Parkinson's disease mice through Nrf2-ARE signaling pathway
| Autor: | Ting-Ting Huang, Lun-Lin Mao, Bo-Na Wu, Dong-Lin Hao, Zhang Jin |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty NF-E2-Related Factor 2 Biophysics Substantia nigra Biology medicine.disease_cause Biochemistry Neuroprotection Hippocampus 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cognition Internal medicine medicine Animals Molecular Biology Inflammation Behavior Animal MPTP Dopaminergic MPTP Poisoning Parkinson Disease Cell Biology Glutathione Malondialdehyde Antioxidant Response Elements Uric Acid Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology Neuroprotective Agents chemistry Uric acid Cytokines 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 493(4) |
| ISSN: | 1090-2104 |
| Popis: | Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1β and decreased serum and hippocampus levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect