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Time resolved ribosome profiling study of oxygen and glucose deprivation of rat pheochromocytoma cells

ABSTRACT: Oxygen and glucose metabolism plays a pivotal role in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) occurs during ischemia and stroke, resulting in extensive tissue injury and cell death. We applied time-resolved ribosome profiling technique to assess early events at the level of gene expression in rat pheochromocytoma PC12 cells during short-term OGD. Most substantial alterations in transcripts levels and their translation were seen to occur in the first 20 minutes of OGD. The rapid adaptation of translation apparatus to OGD is global and involves altered elongation and initiation rates. We also observed salient and reproducible alterations in ribosome densities of individual mRNAs such as increased translation of particular upstream Open Reading Frames (uORFs); induced site-specific arrests of the ribosomes and synthesis of extended protein isoforms.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE60752 | GEO | 2015/04/10

SECONDARY ACCESSION(S): PRJNA259424

REPOSITORIES: GEO

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Time resolved ribosome profiling study of oxygen and glucose deprivation of rat pheochromocytoma cells

Project description:Oxygen and glucose metabolism plays a pivotal role in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) occurs during ischemia and stroke, resulting in extensive tissue injury and cell death. We applied time-resolved ribosome profiling technique to assess early events at the level of gene expression in rat pheochromocytoma PC12 cells during short-term OGD. Most substantial alterations in transcripts levels and their translation were seen to occur in the first 20 minutes of OGD. The rapid adaptation of translation apparatus to OGD is global and involves altered elongation and initiation rates. We also observed salient and reproducible alterations in ribosome densities of individual mRNAs such as increased translation of particular upstream Open Reading Frames (uORFs); induced site-specific arrests of the ribosomes and synthesis of extended protein isoforms. Ribosome profiling (with mRNA-seq sequencing) was carried out at 0,20,40 and 60 minutes of OGD. Two biological replicates were used.

2015-04-10 | E-GEOD-60752 | biostudies-arrayexpress

Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma

Project description:Pheochromocytoma has attracted much attention as a kind of neuroendocrine tumor with the highest genetic correlation in all types of tumors. Detailedly, the frequency of germline mutation in pheochromocytoma is as high as about 40%, and the mutation frequency of von Hippel Lindau (VHL) is the highest in all pheochromocytoma genes. However, the effects of VHL mutation on proteome of pheochromocytoma have remained unexplored. In this study, we compared and analyzed the proteomics of VHL-deficient and VHL WT PC12 cell line. It is showed that expressional level of 434 proteins (fold change > 1.3, VHL shRNA/WT) was significantly changed by VHL deficiency. Furthermore, the functions of these proteins were predicted by gene ontology (GO) and Kyoto Protocol Encyclopedia of Genes and Genomes (KEGG). Of the 434 proteins, 83 proteins, involved in cell proliferation, cell cycle, cell migration, and so on, were interpreted their complex regulatory relationships using String database. More importantly, we discovered 7 novel critical genes whose expression were up-regulated due to VHL deficiency, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2) and Serpin Family E Member 1 (SERPINE1), which may be related to cell proliferation and migration in VHL-mutated pheochromocytoma tumor samples. These results indicate that deficiency of VHL would promote the development of pheochromocytoma by activating expression of genes associated with cell proliferation and migration.

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Effects of polyglutamine expansion and subcellular localization of C-terminal fragment of Cav2.1 in PC12 rat pheochromocytoma cells

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