Dataset Information

Cholesterol depletion increases expression of autophagy-related genes in mink lung Mv1Lu cells

ABSTRACT: Purpose: Employ next generation sequencing (NGS) to study the transcriptomic response to prolonged reduction in the cholesterol level, with emphasis on autophagy-related genes. Methods: Mv1Lu cells were subjected (or not; control) to cholesterol depletion (16 h, with lovastatin and mevalonate in the presence of lipoprotein deficient serum (LPDS), resulting in 30% reduction in the level of free cholesterol). mRNA profiles were generated by deep sequencing, in triplicates, using Illumina NextSeq500. See methods and protocols for details regarding downstream bioinformatic analysis. Results: Using an optimized data analysis workflow sequencing data from lung samples and identified that cholesterol depletion resulted in 2844 and 2822 genes with significantly increased or reduced expression, respectively. The set of differentially expressed genes was significantly enriched with functional annotations relating to cholesterol metabolic regulation and autophagy. These results were correlated with the upregulation of autophagy in biochemical studies. Conclusions: Mild reduction in the cholesterol level leads to a highly significant increase in the expression of multiple autophagy-related genes. The autophagy genes whose expression was modified by cholesterol depletion were scattered onto multiple steps of the autophagy process, and suggested a mainly positive regulation of autophagy by statin treatment.

ORGANISM(S): Neogale vison

PROVIDER: GSE179869 | GEO | 2021/11/03

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:This model is from the article: A model of flux regulation in the cholesterol biosynthesis pathway: Immune mediated graduated flux reduction versus statin-like led stepped flux reduction. Watterson S, Guerriero ML, Blanc M, Mazein A, Loewe L, Robertson KA, Gibbs H, Shui G, Wenk MR, Hillston J, Ghazal P. Biochimie. 2012 Jun 1. 22664637 , Abstract: The cholesterol biosynthesis pathway has recently been shown to play an important role in the innate immune response to viral infection with host protection occurring through a coordinate down regulation of the enzymes catalysing each metabolic step. In contrast, statin based drugs, which form the principle pharmaceutical agents for decreasing the activity of this pathway, target a single enzyme. Here, we build an ordinary differential equation model of the cholesterol biosynthesis pathway in order to investigate how the two regulatory strategies impact upon the behaviour of the pathway. We employ a modest set of assumptions: that the pathway operates away from saturation, that each metabolite is involved in multiple cellular interactions and that mRNA levels reflect enzyme concentrations. Using data taken from primary bone marrow derived macrophage cells infected with murine cytomegalovirus or treated with IFNγ, we show that, under these assumptions, coordinate down-regulation of enzyme activity imparts a graduated reduction in flux along the pathway. In contrast, modelling a statin-like treatment that achieves the same degree of down-regulation in cholesterol production, we show that this delivers a step change in flux along the pathway. The graduated reduction mediated by physiological coordinate regulation of multiple enzymes supports a mechanism that allows a greater level of specificity, altering cholesterol levels with less impact upon interactions branching from the pathway, than pharmacological step reductions. We argue that coordinate regulation is likely to show a long-term evolutionary advantage over single enzyme regulation. Finally, the results from our models have implications for future pharmaceutical therapies intended to target cholesterol production with greater specificity and fewer off target effects, suggesting that this can be achieved by mimicking the coordinated down-regulation observed in immunological responses.

Dataset Information

Cholesterol depletion increases expression of autophagy-related genes in mink lung Mv1Lu cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets