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Lipocalin 2 deficiency inhibits cell proliferation, autophagy, and mitochondrial biogenesis in mouse embryonic cells

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Abstract

Lipocalin 2 (LCN2) has been recently implicated as a critical player in multiple cancer tumorigeneses. However, the molecular mechanisms for its tumorigenic role are poorly understood. Herein, we investigated the effects of LCN2 on cell proliferation, autophagy, and mitochondrial biogenesis in MEF cells. We observed that LCN2 deficiency significantly inhibited cell proliferation and autophagy in MEF cells. Furthermore, mitochondrial DNA content, mRNA expression levels of mitochondrial-encoded gene cytochrome oxidase 2 and PGC-1α were all markedly reduced in LCN2−/− MEF cells. Additionally, when compared with wild-type MEF cells, LCN2−/− MEF cells expressed significantly higher levels of IRS-1, and displayed more potent TNFα-stimulated NF-κB activation. These findings demonstrate that LCN2 is a critical regulator of cell proliferation, autophagy, and mitochondrial biogenesis.

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Abbreviations

MEF:

Mouse embryonic fibroblasts

MTT:

Thiazolyl blue tetrazolium Bromide

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha

IRS-1:

Insulin receptor substrate 1

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Acknowledgments

The project described was supported by Grant Number R01DK080743 (to X.C.) from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health. We thank Wendy Wright from the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota for the technical assistance in establishment of mouse embryonic fibroblasts.

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  1. Department of Food Science and Nutrition, University of Minnesota-Twin Cities, St Paul, MN, 55108-1038, USA

    Daozhong Jin, Yuanyuan Zhang & Xiaoli Chen

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  1. Daozhong Jin
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  2. Yuanyuan Zhang
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  3. Xiaoli Chen
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Correspondence to Xiaoli Chen.

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Jin, D., Zhang, Y. & Chen, X. Lipocalin 2 deficiency inhibits cell proliferation, autophagy, and mitochondrial biogenesis in mouse embryonic cells. Mol Cell Biochem 351, 165–172 (2011). https://doi.org/10.1007/s11010-011-0724-6

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