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Gene expression changes in PC12 cells expressing GFP-mHtt-74Q treated with Guanabenz analogues

ABSTRACT: To gain an overview of the cellular impact of Guanabenz analogues, we analyzed the gene expression changes in PC12 cells expressing GFP-mHtt-74Q utilizing Affimatrix rat genome microarrays. Following exposure of PC12 cells expressing GFP-mHtt-74Q to Compound 6 for 48 hrs, we noted the enhanced expression of over 46 genes and the reduced expression of 8 genes compared to DMSO

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE119557 | GEO | 2019/09/05

REPOSITORIES: GEO

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Project description:During neurogenesis, expression of the basic Helix-Loop-Helix NeuroD6/Nex1/MATH-2 transcription factor parallels neuronal differentiation, while maintaining the differentiated state in the mature nervous system. To further dissect NeuroD6 differentiation properties, we previously generated a NeuroD6-overexpressing stable PC12 cell line, PC12-ND6, which displays a neuronal phenotype characterized by spontaneous neuritogenesis, accelerated NGF-induced differentiation, and increased regenerative capacity. Furthermore, we reported that NeuroD6 promotes long-term neuronal survival upon oxidative stress triggered by serum deprivation. In this study, we identified the NeuroD6-mediated transcriptional regulatory pathways linking neuronal differentiation to survival, by conducting a genome-wide microarray analysis using PC12-ND6 cells and serum deprivation as a stress paradigm. Through a series of filtering steps and a gene-ontology analysis, we found that NeuroD6 promotes distinct but overlapping gene networks, consistent with the differentiation, regeneration, and survival properties of PC12-ND6 cells. Using a gene set enrichment analysis, we provide the first evidence of a compelling link between NeuroD6 and a set of heat shock proteins in the absence of stress, which may be instrumental to confer stress tolerance to PC12-ND6 cells. Immunocytochemistry results showed that HSP27 and HSP70 interact with cytoskeletal elements, consistent with their roles in neuritogenesis and preserving cellular integrity. HSP70 also colocalizes with mitochondria located in the soma, growing neurites and growth cones of PC12-ND6 cells prior to and upon stress stimulus, consistent with its neuroprotective functions. Collectively, our findings support the notion that NeuroD6 links neuronal differentiation to survival via the network of molecular chaperones and endows the cells with increased stress tolerance. Experiment Overall Design: The experimental design involved six replicates of serum-grown PC12 cells (control), serum-grown PC12-ND6 cells (t=0), and serum-deprived PC12-ND6 cells (t=48 hrs).

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Gene expression changes in PC12 cells expressing GFP-mHtt-74Q treated with Guanabenz analogues

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