Cargando…
GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease
The neuromodulator hydrogen sulfide (H(2)S) was shown to exert neuroprotection in different models of Parkinson’s disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H(2)S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671206/ https://www.ncbi.nlm.nih.gov/pubmed/29163149 http://dx.doi.org/10.3389/fphar.2017.00741 |
_version_ | 1783276197417844736 |
---|---|
author | Hou, Xiaoou Yuan, Yuqing Sheng, Yulan Yuan, Baoshi Wang, Yali Zheng, Jiyue Liu, Chun-Feng Zhang, Xiaohu Hu, Li-Fang |
author_facet | Hou, Xiaoou Yuan, Yuqing Sheng, Yulan Yuan, Baoshi Wang, Yali Zheng, Jiyue Liu, Chun-Feng Zhang, Xiaohu Hu, Li-Fang |
author_sort | Hou, Xiaoou |
collection | PubMed |
description | The neuromodulator hydrogen sulfide (H(2)S) was shown to exert neuroprotection in different models of Parkinson’s disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H(2)S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i.p.) administration. Saline was given as a control. Behavioral tests (rotarod, balance beam, and grid walking) showed that 50 mg/kg GYY significantly ameliorated MPTP-caused motor impairments. At lower doses (12.5 and 25 mg/kg) GYY exhibited a less obvious effect. Consistent with this, immunohistochemistry and western blot analysis demonstrated that 50 mg/kg GYY attenuated the loss of tyrosine hydroxylase (TH) positive neurons in the substantia nigra and the decrease of TH expression in the striatum of MPTP-treated mice. Moreover, at this regimen GYY relieved the nitrative stress, as indicated by the decreases in nitric oxide (NO) generation and neuronal NO synthase (nNOS) upregulation elicited by MPTP in the striatum. The suppression of GYY on nNOS expression was verified in vitro, and the results further revealed that Akt activation may participate in the inhibition by GYY on nNOS upregulation. More important, GYY reduced the nitrated modification of α-synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced α-synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD. |
format | Online Article Text |
id | pubmed-5671206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56712062017-11-21 GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease Hou, Xiaoou Yuan, Yuqing Sheng, Yulan Yuan, Baoshi Wang, Yali Zheng, Jiyue Liu, Chun-Feng Zhang, Xiaohu Hu, Li-Fang Front Pharmacol Pharmacology The neuromodulator hydrogen sulfide (H(2)S) was shown to exert neuroprotection in different models of Parkinson’s disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H(2)S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i.p.) administration. Saline was given as a control. Behavioral tests (rotarod, balance beam, and grid walking) showed that 50 mg/kg GYY significantly ameliorated MPTP-caused motor impairments. At lower doses (12.5 and 25 mg/kg) GYY exhibited a less obvious effect. Consistent with this, immunohistochemistry and western blot analysis demonstrated that 50 mg/kg GYY attenuated the loss of tyrosine hydroxylase (TH) positive neurons in the substantia nigra and the decrease of TH expression in the striatum of MPTP-treated mice. Moreover, at this regimen GYY relieved the nitrative stress, as indicated by the decreases in nitric oxide (NO) generation and neuronal NO synthase (nNOS) upregulation elicited by MPTP in the striatum. The suppression of GYY on nNOS expression was verified in vitro, and the results further revealed that Akt activation may participate in the inhibition by GYY on nNOS upregulation. More important, GYY reduced the nitrated modification of α-synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced α-synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD. Frontiers Media S.A. 2017-10-30 /pmc/articles/PMC5671206/ /pubmed/29163149 http://dx.doi.org/10.3389/fphar.2017.00741 Text en Copyright © 2017 Hou, Yuan, Sheng, Yuan, Wang, Zheng, Liu, Zhang and Hu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Hou, Xiaoou Yuan, Yuqing Sheng, Yulan Yuan, Baoshi Wang, Yali Zheng, Jiyue Liu, Chun-Feng Zhang, Xiaohu Hu, Li-Fang GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title | GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title_full | GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title_fullStr | GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title_full_unstemmed | GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title_short | GYY4137, an H(2)S Slow-Releasing Donor, Prevents Nitrative Stress and α-Synuclein Nitration in an MPTP Mouse Model of Parkinson’s Disease |
title_sort | gyy4137, an h(2)s slow-releasing donor, prevents nitrative stress and α-synuclein nitration in an mptp mouse model of parkinson’s disease |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671206/ https://www.ncbi.nlm.nih.gov/pubmed/29163149 http://dx.doi.org/10.3389/fphar.2017.00741 |
work_keys_str_mv | AT houxiaoou gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT yuanyuqing gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT shengyulan gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT yuanbaoshi gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT wangyali gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT zhengjiyue gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT liuchunfeng gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT zhangxiaohu gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease AT hulifang gyy4137anh2sslowreleasingdonorpreventsnitrativestressandasynucleinnitrationinanmptpmousemodelofparkinsonsdisease |