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Effect of Pak4 ablation on transcriptome in liver of fasted mice

ABSTRACT: Effect of Pak4 ablation on transcriptome in liver of fasted mice

PROVIDER: PRJNA885417 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21752714_1.fastq.gz	Fastqsanger.gz
	SRR21752714_2.fastq.gz	Fastqsanger.gz
	SRR21752715_1.fastq.gz	Fastqsanger.gz
	SRR21752715_2.fastq.gz	Fastqsanger.gz
	SRR21752716_1.fastq.gz	Fastqsanger.gz

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Effect of Pak4 ablation on transcriptome in liver of fasted mice

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Effect of Pak4 deficiency on transcriptome in liver of mice

Project description:PAK4 has emerged as a promising target for anti-cancer drug development. However, its role in oxidative stress conditions remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. To elucidate molecular mechanisms, we performed RNA-sequencing analysis using littermate WT and hepatocyte-specific Pak4 KO mice in I/R condition. Transcriptomic analysis enabled us to find the main signaling nodes altered by Pak4 deficiency in close association with antioxidant response.

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Project description:RNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism.

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