ABSTRACT
Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.
ABSTRACT
We studied the protective effect and mechanism of isorhamnetin (ISO) on 1-methyl-4-phenylpyridiniumion (MPP+)-induced SH-SY5Y cells injury. MPP+-induced SH-SY5Y cell injury model was established, and cell viability was measured by MTT and LDH methods. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in cells were determined to investigate the level of oxidative stress. DCFH-DA and MitoSOX fluorescence probes were used to detect the levels of intracellular reactive oxygen species (ROS) and mitochondria superoxide, respectively. JC-1 fluorescence probe was used to detect the changes of mitochondrial membrane potential. Western blot and immunofluorescence methods were used to determine the expressions of Sirt1 and PGC-1 proteins, as well as the expression levels of apoptosis-related proteins Bax and Bcl-2. MPP+ at the dose of 500 μmol·L-1 significantly reduced SH-SY5Y cells viability to 52.46% and increased LDH release to 417.63%. ISO at 5 and 15 μmol·L-1 significantly increased the expression of Sirt1 and PGC-1α, inhibited LDH release, reduced intracellular ROS and mitochondria superoxide, inhibited the decline of mitochondrial membrane potential and increased cell viability to 61.61% and 67.55%. In addition, ISO could downregulate the expression of Bax and upregulate the expression of Bcl-2 to reduce cell apoptosis. ISO-mediated inhibition of apoptosis could be reversed by Sirt1 specific inhibitor Sirtinol. Through activating Sirt1/PGC-1α signaling pathway, ISO could reduce oxidative stress injury and inhibit cell apoptosis to protect cells from MPP+ injury.
ABSTRACT
Aim To investigate the effects of salvianol-ic acid D ( SalD) on mitochondrial function and bio- synthesis in SH-SY5Y cells after MPP+injury and the possible mechanisms. Methods The cell model was established by MPP+injury in SH-SY5Y cells. The cytotoxicity of MPP+was detected by MTT assay. The effects of SalD on viability of SH-SY5Y cells were ex-amined by MTT and LDH assay. The apoptosis of SH-SY5Y cells was detected by AO/EB assay. The levels of ROS and mitochondrial superoxide were determined using DCFH-DA and MitoSOX probes, respectively. Mitochondrial function was examined by measuring ATP level and mitochondrial membrane potential. The levels of PGC-1α and its downstream regulatory genes NRF1 and TFAM mRNA were detected by qPCR. The protein levels of PGC-1α, NRF1 and TFAM in cells were detected by Western blot and immunofluorescence assays. Results MPP+injury resulted in a significant reduction of cell viability to 51.34%. 0.1, 1, 5 μmol ·L-1SalD and 5 mmol·L-1NAC could reduce MPP+-induced SH-SY5Y cell injury and LDH release. The cell viability increased to 67.98% , 71.79% , 76.91% and 77.55% , respectively. Moreover, SalD could reduce the increase of intracellular ROS and mi-tochondrial superoxide induced by MPP+, decrease mitochondrial membrane potential and improve mito-chondrial function. SalD also significantly increased both the transcription and expression levels of PGC-1α, NRF1 and TFAM. Conclusion SalD could in-hibit MPP+-induced SH-SY5Y cell injury and improve mitochondrial function and mitochondrial biosynthesis.
ABSTRACT
AIM@#To investigate the effects of pinocembrin on angiotensin II (Ang II)-induced vascular contraction, and to explore its molecular mechanism of actions.@*METHODS@#The isometric vascular tone was measured in rat thoracic aortic rings with denuded endothelium. Phosphorylation level of myosin phosphatase target unit 1 (MYPT1), and protein levels of Rho kinase 1 (ROCK1, ROKβ or p160ROCK) and angiotensin II type-1 receptor (AT1R) were determined by Western blot analysis.@*RESULTS@#Pinocembrin produced a relaxant effect on endothelium-denuded aortic rings contracted by Ang II (100 nmol·L(-1)) in a dose-dependent manner. In endothelium-denuded aortic rings stimulated by Ang II, pretreatment with pinocembrin (25 and 100 μmol·L(-1)) for 20 min significantly attenuated MYPT1 phosphorylation and ROCK1 protein levels. Meanwhile, the protein level of AT1R in response to Ang II was not affected by pinocembrin in rat aortic rings.@*CONCLUSION@#These findings indicate that pinocembrin inhibits vasoconstriction induced by Ang II in rat endothelium-denuded aortic rings, and the mechanism at least in part, is due to the blockade of the RhoA/ROCK pathway.