| Parkinson' disease is a neurodegenerative disease mainly caused by the damage of dopaminergic nigrostriatal neurons and its etiology is unclear up to now, maybe involved in the influence of several factors such genetics and environment. An inhibitor of mitochondrial respiratory chain , 1-methyl-4-phenyl pyridinium ion(MPP+) can cause damage to dopaminergic neurons , so can its chemical analogue paraquat. The rat pheochromocytoma PC12 cell strain has the characteristics of dopaminergic neurons, so it is often used for the study of toxication of MPP+ and paraquat. One of the most difficult problem in the treatment of PD is how to protect dopaminergic neurons. L-deprenyl has been shown to have a good neuroprotective effect as a monoamine oxidase B inhibitor in vitro experiments. Some neurotrophic factors can also protect the vulnerable neurons and support their normal function in the degenerative disease. It has been proved that basic fibroblast growth factor(bFGF) can protect dopaminergic neurons in animal models, with the induction of activin expression essential for its protection. Glial cell line-derived neurotrophic factor(GDNF) is well known for its potent neuroprotective effect on dopaminergic neurons in nigrostriatal system, with the same neurotrophic effect as activin A. Activin A is one of the members of transforming growth factor β(TGF-β) superfamily, formed by two subunits of βA-βA. There are also activin B and activin AB in activin family, formed by βB-βB and βA-βB respectively. Recent works indicated that the expression of activin βA mRNA in hippocampi or dental gyri was upregulated following the injury of ischemia, trauma, and excitotoxin , while the activin βB mRNA is unchanged and the level of activin receptor IIA(Act RIIA) was downregulated. It was also shown that exogenous application of recombinant human activin A (rhAct A) can protect neurons within these regions, indicating that activin A may be a neuroprotective factor. But, there is no report about how the different subunits and receptors of activin change following the injury of paraquat and MPP+ ; reports on whether the exogenous application of activin A can provide protection for dopaminergic neurons against the injury of paraquat and MPP+ are rarely seen, nor there is any report on what the mechanism of activin protection is. So it will be important to explore the protective effect of activin A on dopaminergic neurons before knowing the mechanism of PD and finding a new therapeutic approach. In this study, the dynamic change of expression of activin βA, activin βB and Act RIIA mRNA in PC12 cells was observed following the injury of paraquat and MPP+ with the use of reverse transcriptase –polymerase chain reaction (RT-PCR) method, also the viability of cells was studied with tyrpan blue staining method. Then we pretreated PC12 cells with rhAct A and L-Deprenyl 24 hours before adding MPP+ and paraquat, to observe the change of viability of cells with MTT method; to assay the change of level of cellular tyrosine hydroxylase(TH) protein and Bcl-2 protein with immunocytochemistry; to assay the change of expression of TH mRNA and Bcl-2 mRNA with RT-PCR method; to evaluate the change of apoptotic cells with terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) method. we contrasted the results of activin A group and L-Deprenyl group with paraquat group, as well as with MPP+ group, so that we can investigate the protective effect and possible mechanism of activin A against the injury of paraquat and MPP+ . Results: 1. At the points of 3 h, 6 h, 12 h and 24 h following the injury in the groups of paraquat and MPP+, the expression of activin βA, activin βB and Act RIIA mRNA showed a trend of gradual decline with the injury going on in PC12 cells,with the expression begining to decrease at the point of 3 h and decrease to the lowest 24 hours following the injury. In contrast, in control group , no detectable changes were observed for the expression of activin βA, activin βB and Act RIIA mRNA...
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