机构：[1]Institute of Neuroscience, Soochow University, Suzhou, China,[2]Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China,[3]Department of Pharmacology, School of Pharmacy, Soochow University, Suzhou, China,[4]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China
The neuromodulator hydrogen sulfide (H2S) 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 H2S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4phenyl- 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 a -synuclein, a PD-related protein, in MPTP-induced mice. Overall, our findings suggest that GYY attenuated dopaminergic neuron degeneration and reduced a -synuclein nitration in the midbrain, thus exerting neuroprotection in MPTP-induced mouse model of PD.
基金：
This work was supported by grants from the National Key
Plan for Scientific Research and Development of China (No.
2016YFC1306002), National Natural Science Foundation of
China (Nos. 81171212, 81571233), and the Natural Science
Foundation of Jiangsu Province of China (No. BK2011294). This
was also partly supported by Suzhou Clinical Research Center
of Neurological Disease (Szzx201503) and the Priority Academic
Program Development of Jiangsu Higher Education Institutions
(PAPD).
第一作者机构：[1]Institute of Neuroscience, Soochow University, Suzhou, China,[2]Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China,
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Neuroscience, Soochow University, Suzhou, China,[2]Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China,[4]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China
推荐引用方式(GB/T 7714)：
Xiaoou Hou,Yuqing Yuan,Yulan Sheng,et al.GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and alpha-Synuclein Nitration in an MPTP Mouse Model of Parkinson's Disease[J].FRONTIERS IN PHARMACOLOGY.2017,8(OCT):741.doi:10.3389/fphar.2017.00741.
APA：
Xiaoou Hou,Yuqing Yuan,Yulan Sheng,Baoshi Yuan,Yali Wang...&Li-Fang Hu.(2017).GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and alpha-Synuclein Nitration in an MPTP Mouse Model of Parkinson's Disease.FRONTIERS IN PHARMACOLOGY,8,(OCT)
MLA：
Xiaoou Hou,et al."GYY4137, an H2S Slow-Releasing Donor, Prevents Nitrative Stress and alpha-Synuclein Nitration in an MPTP Mouse Model of Parkinson's Disease".FRONTIERS IN PHARMACOLOGY 8..OCT(2017):741
