The metabolomics of a protein kinase C delta (PKC$δ$) knock-out mouse model. Loots, D. T., Adeniji, A. A., Van Reenen, M., Ozturk, M., Brombacher, F., & Parihar, S. P Metabolomics, 18(11):92, NLM (Medline), nov, 2022.
The metabolomics of a protein kinase C delta (PKC$δ$) knock-out mouse model [link]Paper  doi  abstract   bibtex   
INTRODUCTION: PKC$δ$ is ubiquitously expressed in mammalian cells and its dysregulation plays a key role in the onset of several incurable diseases and metabolic disorders. However, much remains unknown about the metabolic pathways and disturbances induced by PKC deficiency, as well as the metabolic mechanisms involved. OBJECTIVES: This study aims to use metabolomics to further characterize the function of PKC from a metabolomics standpoint, by comparing the full serum metabolic profiles of PKC deficient mice to those of wild-type mice. METHODS: The serum metabolomes of PKC$δ$ knock-out mice were compared to that of a wild-type strain using a GCxGC-TOFMS metabolomics research approach and various univariate and multivariate statistical analyses. RESULTS: Thirty-seven serum metabolite markers best describing the difference between PKC$δ$ knock-out and wild-type mice were identified based on a PCA power value \textgreater 0.9, a t-test p-value \textless 0.05, or an effect size \textgreater 1. XERp prediction was also done to accurately select the metabolite markers within the 2 sample groups. Of the metabolite markers identified, 78.4% (29/37) were elevated and 48.65% of these markers were fatty acids (18/37). It is clear that a total loss of PKC$δ$ functionality results in an inhibition of glycolysis, the TCA cycle, and steroid synthesis, accompanied by upregulation of the pentose phosphate pathway, fatty acids oxidation, cholesterol transport/storage, single carbon and sulphur-containing amino acid synthesis, branched-chain amino acids (BCAA), ketogenesis, and an increased cell signalling via N-acetylglucosamine. CONCLUSION: The charaterization of the dysregulated serum metabolites in this study, may represent an additional tool for the early detection and screening of PKC$δ$-deficiencies or abnormalities.
@article{Loots2022,
abstract = {INTRODUCTION: PKC$\delta$ is ubiquitously expressed in mammalian cells and its dysregulation plays a key role in the onset of several incurable diseases and metabolic disorders. However, much remains unknown about the metabolic pathways and disturbances induced by PKC deficiency, as well as the metabolic mechanisms involved. OBJECTIVES: This study aims to use metabolomics to further characterize the function of PKC from a metabolomics standpoint, by comparing the full serum metabolic profiles of PKC deficient mice to those of wild-type mice. METHODS: The serum metabolomes of PKC$\delta$ knock-out mice were compared to that of a wild-type strain using a GCxGC-TOFMS metabolomics research approach and various univariate and multivariate statistical analyses. RESULTS: Thirty-seven serum metabolite markers best describing the difference between PKC$\delta$ knock-out and wild-type mice were identified based on a PCA power value {\textgreater} 0.9, a t-test p-value {\textless} 0.05, or an effect size {\textgreater} 1. XERp prediction was also done to accurately select the metabolite markers within the 2 sample groups. Of the metabolite markers identified, 78.4{\%} (29/37) were elevated and 48.65{\%} of these markers were fatty acids (18/37). It is clear that a total loss of PKC$\delta$ functionality results in an inhibition of glycolysis, the TCA cycle, and steroid synthesis, accompanied by upregulation of the pentose phosphate pathway, fatty acids oxidation, cholesterol transport/storage, single carbon and sulphur-containing amino acid synthesis, branched-chain amino acids (BCAA), ketogenesis, and an increased cell signalling via N-acetylglucosamine. CONCLUSION: The charaterization of the dysregulated serum metabolites in this study, may represent an additional tool for the early detection and screening of PKC$\delta$-deficiencies or abnormalities.},
author = {Loots, Du Toit and Adeniji, Adetomiwa Ayodele and {Van Reenen}, Mari and Ozturk, Mumin and Brombacher, Frank and Parihar, Suraj P},
doi = {10.1007/S11306-022-01949-W/FIGURES/4},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Loots et al. - 2022 - The metabolomics of a protein kinase C delta (PKC$\delta$) knock-out mouse model.pdf:pdf},
issn = {15733890},
journal = {Metabolomics},
keywords = {Auto-immune diseases,Diagnostic biomarker,Metabolic disorder,Metabolomics,Non-communicable disease,OA,OA{\_}PMC,Protein kinase C,Serum samples,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {nov},
number = {11},
pages = {92},
pmid = {36371785},
publisher = {NLM (Medline)},
title = {{The metabolomics of a protein kinase C delta (PKC$\delta$) knock-out mouse model}},
url = {https://link.springer.com/article/10.1007/s11306-022-01949-w},
volume = {18},
year = {2022}
}

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