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NIPSNAP1 deficient mice exhibit altered liver amino acid, lipid and nucleotide metabolism

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Abstract

4-Nitrophenyl phosphatase domain and non-neuronal SNAP25-like protein homolog1 (NIPSNAP1) is an evolutionarily conserved protein found in a variety of species ranging from C. elegans to human. NIPSNAP1 protein is localized in mitochondria and is highly expressed in liver, brain and kidney. The molecular and cellular roles of NIPSNAP1 are still unknown. To gain insights into the function of NIPSNAP1, we generated a mouse model with a disruption of Nipsnap1 gene and performed metabolomic analysis on their liver tissues. Liver samples from 13 to 15 month old NIPSNAP1 deficient (n = 7) and wild-type (n = 8) mice were extracted and processed for analysis using liquid/gas chromatography followed by mass spectrometry (LC/MS and GC/MS). We examined a total of 291 compounds in liver samples and found 45 compounds whose levels were significantly altered (p < 0.05, Welch’s t test) in NIPSNAP1 deficient mice compared to controls. These compounds were associated with a variety of processes, including metabolism of nucleotides, amino acids and lipids. In addition, we found a significant reduction in reduced glutathione (GSH) (0.63-fold change, p < 0.05) and elevation in cysteine–glutathione disulfide (2.77-fold change, p < 0.05). Our results suggest that NIPSNAP1 deficiency affects multiple processes in intermediate metabolism and results in oxidative stress in the liver.

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Acknowledgments

We are grateful to S. Bass and M. Perez for technical assistance and mouse colony management. This work was supported by Assisi Foundation of Memphis and the University of Memphis FedEx Institute of Technology.

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Authors and Affiliations

  1. Department of Biological Sciences, University of Memphis, 3774 Walker Ave, 429 Smith Hall, Memphis, TN, 38152, USA

    Sarani Ghoshal, Lynn Jones & Ramin Homayouni

  2. Center for Translational Informatics, University of Memphis, Memphis, TN, 38152, USA

    Ramin Homayouni

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  1. Sarani Ghoshal
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  2. Lynn Jones
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  3. Ramin Homayouni
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Correspondence to Ramin Homayouni.

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Ghoshal, S., Jones, L. & Homayouni, R. NIPSNAP1 deficient mice exhibit altered liver amino acid, lipid and nucleotide metabolism. Metabolomics 10, 250–258 (2014). https://doi.org/10.1007/s11306-013-0583-0

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