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Acta Pharmaceutica Sinica ; (12): 843-848, 2014.
Article in Chinese | WPRIM | ID: wpr-245005

ABSTRACT

To investigate vincristine-induced dopaminergic neurons toxicity and mechanism, and explore the molecular target to reduce the toxicity, zebrafish was chosen as a model animal, based on RT-PCR, Western blotting, whole mount in situ immunofluorescence and other technical means. The results showed that the transcription levels of tyrosine hydroxylase gene and dopamine transporter protein gene were inhibited. Furthermore, the number of dopaminergic neurons was decreased by vincristine. Autophagy was suppressed and beclin1 gene expression was inhibited in a dose-dependent manner by vincristine in larval zebrafish. Up-regulated beclin1 partly reduced vincristine-induced neurotoxicity, and down-regulated beclin1 increased toxicity. Beclin1 plays an important role in vincristine-induced dopaminergic neurons toxicity.


Subject(s)
Animals , Apoptosis Regulatory Proteins , Metabolism , Autophagy , Dopaminergic Neurons , Pathology , Dose-Response Relationship, Drug , Down-Regulation , Gene Expression Regulation , Larva , Tyrosine 3-Monooxygenase , Metabolism , Vincristine , Zebrafish , Zebrafish Proteins , Metabolism
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