Ghoshal, S. Nipsnap1 Deficient Mice Exhibit Altered Liver Amino Acid, Lipid and Nucleotide Metabolism. Metabolomics, 2014.


4-Nitrophenyl phosphatase domain and nonneuronal 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 metabolomics 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 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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