Toxicological Research

  • 제33권3호
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  • Pages.219-224
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  • 2017
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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Induction of Lipin1 by ROS-Dependent SREBP-2 Activation

  • 투고 : 2017.04.25
  • 심사 : 2017.06.12
  • 발행 : 2017.07.15
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초록

Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key role in lipid metabolism. Since free radicals contribute to metabolic diseases in the liver, this study investigated the effects of free radicals on the regulation of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT-PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP-1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was significantly reduced by N-acetyl-$\small{L}$-cysteine treatment, indicating that reactive oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated whether the hypoxic environments that cause endogenous ROS production in mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to hypoxia also increased Lipin1 expression. In contrast, pretreatment with antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our results show that ROS activate SREBP-2, which induces Lipin1 expression.

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참고문헌

  1. Liska, D.J. (1998) The detoxification enzyme systems. Altern. Med. Rev., 3, 187-198.
  2. Cichoz-Lach, H. and Michalak, A. (2014) Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol., 20, 8082-8091. https://doi.org/10.3748/wjg.v20.i25.8082
  3. Fernandez-Sanchez, A., Madrigal-Santillan, E., Bautista, M., Esquivel-Soto, J., Morales-Gonzalez, A., Esquivel-Chirino, C., Durante-Montiel, I., Sanchez-Rivera, G., Valadez-Vega, C. and Morales-Gonzalez, J.A. (2011) Inflammation, oxidative stress, and obesity. Int. J. Mol. Sci., 12, 3117-3132. https://doi.org/10.3390/ijms12053117
  4. West, I.C. (2000) Radicals and oxidative stress in diabetes. Diabet. Med., 17, 171-180. https://doi.org/10.1046/j.1464-5491.2000.00259.x
  5. Chen, Y., Rui, B.B., Tang, L.Y. and Hu, C.M. (2015) Lipin family proteins-key regulators in lipid metabolism. Ann. Nutr. Metab., 66, 10-18.
  6. Reue, K. and Dwyer, J.R. (2009) Lipin proteins and metabolic homeostasis. J. Lipid Res., 50, S109-S114. https://doi.org/10.1194/jlr.R800052-JLR200
  7. Reue, K. and Brindley, D.N. (2008) Thematic review series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism. J. Lipid Res., 49, 2493-2503. https://doi.org/10.1194/jlr.R800019-JLR200
  8. Donkor, J., Zhang, P., Wong, S., O'Loughlin, L., Dewald, J., Kok, B.P., Brindley, D.N. and Reue, K. (2009) A conserved serine residue is required for the phosphatidate phosphatase activity but not the transcriptional coactivator functions of Lipin-1 and Lipin-2. J. Biol. Chem., 284, 29968-29978. https://doi.org/10.1074/jbc.M109.023663
  9. Donkor, J., Sariahmetoglu, M., Dewald, J., Brindley, D.N. and Reue, K. (2007) Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J. Biol. Chem., 282, 3450-3457.
  10. Peterfy, M., Phan, J., Xu, P. and Reue, K. (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat. Genet., 27, 121-124. https://doi.org/10.1038/83685
  11. Finck, B.N., Gropler, M.C., Chen, Z., Leone, T.C., Croce, M.A., Harris, T.E., Lawrence, J.C., Jr. and Kelly, D.P. (2006) Lipin 1 is an inducible amplifier of the hepatic PGC-$1{\alpha}$/$PPAR{\alpha}$ regulatory pathway. Cell Metab., 4, 199-210 https://doi.org/10.1016/j.cmet.2006.08.005
  12. Kim, H.E., Bae, E., Jeong, D.Y., Kim, M.J., Jin, W.J., Park, S.W., Han, G.S., Carman, G.M., Koh, E. and Kim, K.S. (2013) Lipin1 regulates $PPAR{\gamma}$ transcriptional activity. Biochem. J., 453, 49-60. https://doi.org/10.1042/BJ20121598
  13. Bou Khalil, M., Blais, A., Figeys, D. and Yao, Z. (2010) Lipin - The bridge between hepatic glycerolipid biosynthesis and lipoprotein metabolism. Biochim. Biophys. Acta, 1801, 1249-1259. https://doi.org/10.1016/j.bbalip.2010.07.008
  14. Mylonis, I., Sembongi, H., Befani, C., Liakos, P., Siniossoglou, S. and Simos, G. (2012) Hypoxia causes triglyceride accumulation by HIF-1-mediated stimulation of lipin 1 expression. J. Cell Sci., 125, 3485-3493. https://doi.org/10.1242/jcs.106682
  15. Langner, C.A., Birkenmeier, E.H., Ben-Zeev, O., Schotz, M.C., Sweet, H.O., Davisson, M.T. and Gordon, J.I. (1989) The fatty liver dystrophy (fld) mutation. A new mutant mouse with a developmental abnormality in triglyceride metabolism and associated tissue-specific defects in lipoprotein lipase and hepatic lipase activities. J. Biol. Chem., 264, 7994-8003.
  16. Lindegaard, B., Larsen, L.F., Hansen, A.B., Gerstoft, J., Pedersen, B.K. and Reue, K. (2007) Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy. Int. J. Obes. (Lond.), 31, 449-456. https://doi.org/10.1038/sj.ijo.0803434
  17. Seo, K., Yang, J.H., Kim, S.C., Ku, S.K., Ki, S.H. and Shin, S.M. (2014) The antioxidant effects of isorhamnetin contribute to inhibit COX-2 expression in response to inflammation: a potential role of HO-1. Inflammation, 37, 712-722. https://doi.org/10.1007/s10753-013-9789-6
  18. Shin, S.M. and Kim, S.G. (2009) Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3-thione congeners. Mol. Pharmacol., 75, 242-253. https://doi.org/10.1124/mol.108.051128
  19. Eberle, D., Hegarty, B., Bossard, P., Ferre, P. and Foufelle, F. (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie, 86, 839-848. https://doi.org/10.1016/j.biochi.2004.09.018
  20. Schonenberger, M.J. and Kovacs, W.J. (2015) Hypoxia signaling pathways: modulators of oxygen-related organelles. Front. Cell Dev. Biol., 3, 42.
  21. Chen, Y., Liu, J.M., Xiong, X.X., Qiu, X.Y., Pan, F., Liu, D., Lan, S.J., Jin, S., Yu, S.B. and Chen, X.Q. (2015) Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP. Oncotarget, 6, 6406-6421. https://doi.org/10.18632/oncotarget.3444
  22. Hou, J., Cui, A., Song, P., Hua, H., Luo, T. and Jiang, Y. (2015) Reactive oxygen species-mediated activation of the Src-epidermal growth factor receptor-Akt signaling cascade prevents bortezomib-induced apoptosis in hepatocellular carcinoma cells. Mol. Med. Rep., 11, 712-718. https://doi.org/10.3892/mmr.2014.2736
  23. Kretzmann, N.A., Chiela, E., Matte, U., Marroni, N. and Marroni, C.A. (2012) N-acetylcysteine improves antitumoural response of Interferon alpha by NF-${\kappa}B$ downregulation in liver cancer cells. Comp. Hepatol., 11, 4. https://doi.org/10.1186/1476-5926-11-4
  24. Pittner, R.A., Fears, R. and Brindley, D.N. (1985) Effects of cyclic AMP, glucocorticoids and insulin on the activities of phosphatidate phosphohydrolase, tyrosine aminotransferase and glycerol kinase in isolated rat hepatocytes in relation to the control of triacylglycerol synthesis and gluconeogenesis. Biochem. J., 225, 455-462. https://doi.org/10.1042/bj2250455
  25. Pittner, R.A., Fears, R. and Brindley, D.N. (1985) Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes. Biochem. J., 230, 525-534. https://doi.org/10.1042/bj2300525
  26. Whiting, P.H., Bowley, M., Sturton, R.G., Pritchard, P.H., Brindley, D.N. and Hawthorne, J.N. (1977) The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver. Biochem. J., 168, 147-153. https://doi.org/10.1042/bj1680147
  27. Brindley, D.N., Cooling, J., Glenny, H.P., Burditt, S.L. and McKechnie, I.S. (1981) Effects of chronic modification of dietary fat and carbohydrate on the insulin, corticosterone and metabolic responses of rats fed acutely with glucose, fructose or ethanol. Biochem. J., 200, 275-283. https://doi.org/10.1042/bj2000275
  28. Sturton, R.G., Pritchard, P.H., Han, L.Y. and Brindley, D.N. (1978) The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol. Biochem. J., 174, 667-670. https://doi.org/10.1042/bj1740667
  29. Mangiapane, E.H., Lloyd-Davies, K.A. and Brindley, D.N. (1973) A study of some enzymes of glycerolipid biosynthesis in rat liver after subtotal hepatectomy. Biochem. J., 134, 103-112. https://doi.org/10.1042/bj1340103
  30. Hirotsu, Y., Hataya, N., Katsuoka, F. and Yamamoto, M. (2012) NF-E2-related factor 1 (Nrf1) serves as a novel regulator of hepatic lipid metabolism through regulation of the Lipin1 and PGC-$1{\beta}$ genes. Mol. Cell. Biol., 32, 2760-2770. https://doi.org/10.1128/MCB.06706-11
  31. Han, J.Y., Park, S.H., Yang, J.H., Kim, M.G., Cho, S.S., Yoon, G., Cheon, S.H. and Ki, S.H. (2014) Licochalcone suppresses $LXR{\alpha}$-Induced hepatic lipogenic gene expression through AMPK/Sirt1 pathway activation. Toxicol. Res., 30, 19-25. https://doi.org/10.5487/TR.2014.30.1.019
  32. Hu, M., Wang, F., Li, X., Rogers, C.Q., Liang, X., Finck, B.N., Mitra, M.S., Zhang, R., Mitchell, D.A. and You, M. (2012) Regulation of hepatic Lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice. Hepatology, 55, 437-446. https://doi.org/10.1002/hep.24708
  33. Ishimoto, K., Nakamura, H., Tachibana, K., Yamasaki, D., Ota, A., Hirano, K., Tanaka, T., Hamakubo, T., Sakai, J., Kodama, T. and Doi, T. (2009) Sterol-mediated regulation of human Lipin 1 gene expression in hepatoblastoma cells. J. Biol. Chem., 284, 22195-22205. https://doi.org/10.1074/jbc.M109.028753
  34. Furuta, E., Pai, S.K., Zhan, R., Bandyopadhyay, S., Watabe, M., Mo, Y.Y., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Kamada, S., Saito, K., Iiizumi, M., Liu, W., Ericsson, J. and Watabe, K. (2008) Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res., 68, 1003-1011. https://doi.org/10.1158/0008-5472.CAN-07-2489
  35. Bou Khalil, M., Sundaram, M., Zhang, H.Y., Links, P.H., Raven, J.F., Manmontri, B., Sariahmetoglu, M., Tran, K., Reue, K., Brindley, D.N. and Yao, Z. (2009) The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic VLDL. J. Lipid Res., 50, 47-58. https://doi.org/10.1194/jlr.M800204-JLR200

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