Biomolecules & Therapeutics  
Nuclear Receptor PPARα Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKKβ-Deficient Mice
Taehyeong Kim1, Lilik Duwi Wahyudi2, Frank J. Gonzalez1 and Jung-Hwan Kim1,2,*
1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, 2Department of Pharmacology and Graduate School of Convergence Medical Science, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea
E-mail: junghwan.kim@gnu.ac.kr
Tel: +82-55-772-8072, Fax: +82-55-772-8079
Received: September 22, 2016; Revised: November 15, 2016; Accepted: December 6, 2016; Published online: February 13, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Inhibitor of nuclear factor kappa-B kinase beta (IKKβ) plays a critical role in cell proliferation and inflammation in various cells by activating NF-κB signaling. However, the interrelationship between Peroxisome proliferator-activated receptor α (PPARα) and IKKβ in cell proliferation is not clear. In this study, we investigated the possible role of PPARα in the hepatic cell death in the absence of IKKβ gene using liver-specific Ikkb-null (IkkbF/F-AlbCre) mice. To examine the function of PPARα activation in hepatic cell death, wild-type (IkkbF/F) and IkkbF/F-AlbCre mice were treated with PPARα agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the IkkbF/F-AlbCre mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and IkkbF/F-AlbCre mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that IKKβ-derived hepatic apoptosis could be altered by PPARα activation in conjunction with activation of NF-κB and STAT3 signaling.
Keywords: PPARa, IKKb, NF-kB, Wy-14,643, STAT3
References
  1. (2009) The ASTER spectral library version 2.0. Remote Sensing of Environment, 113(4), 711-715. Bishop, J.L., Lane, M.D., Dyar, M.D., and Brown, A.J. (2008) Reflectance and emission spectroscopy study of four groups of phyllosilicates: Smectites, kaolinite- serpentines, chlorites and micas. Clay Minerals, 43(1), 35-54. Bradl, H.B. (2004) Adsorption of heavy metal ions on soils and soils constituents. Journal of Colloid and Interface Science, 277(1), 1-18. Choe, E., van der Meer, F., van Ruitenbeek, F., van der Werff, H., de Smeth, B., and Kim, K.W. (2008) Mapping of heavy metal pollution in stream sediments using combined geochemistry, field spectroscopy, and hyperspectral remote sensing: A case study of the Rodalquilar mining area, SE Spain. Remote Sensing of Environment, 112(7), 3222-3233. Choe, E.Y., Hong, S.Y., Kim, K.W., Kim, Y.H., and Zhang, Y.S. (2010) Monitoring of Soil Properties using VNIR Spectroscopy. Korean Society of Soil Science and Fertilizer, 94-103 (in Korean). Choi, S.G., Park, S.J., Lee, P.K., and Kim, C.S. (2004) An overview of geoenvironmental implications of mineral deposits in Korea. The Korean Society of Economic and Environmental Geology, 37, 1-19 (in Korean). Choi, S.J., Kim, C.H., and Lee, S.G. (2009) Comparison of the Heavy Metal Analysis in Soil Samples by Bench-Top ED-XRF and Field-Potable XRF. Analytical Science and Technology, 22(4), 293-301 (in Korean with English abstract). Clark, R.N., Swayze, G.A., Wise, R., Livo, K.E., Hoefen, T., Kokaly, R.F., and Sutley, S.J. (2007) USGS digital spectral library splib06a. US Geological Survey, Digital Data Series, 231. Hauff, P. (2008) An overview of VIS-NIR-SWIR field spectroscopy as applied to precious metals exploration. Spectral International Inc, 80001, 303-403. Herrmann, W., Blake, M., Doyle, M., Huston, D., Kamprad, J., Merry, N., and Pontual, S. (2001) Short wavelength infrared (SWIR) spectral analysis of hydrothermal alteration zones associated with base metal sulfide deposits at Rosebery and Western Tharsis, Tasmania, and Highway-Reward, Queensland. Economic Geology, 96(5), 939-955. Hu, W., Huang, B., Weindorf, D.C., and Chen, Y. (2014) Metals analysis of agricultural soils via portable X-ray fluorescence spectrometry. Bulletin of environmental contamination and toxicology, 92(4), 420-426. Hyun, H,J., Hwag, U.D., Kim, Y.I., Lee, K.H., and Han, J.G. (2010) Gold Mines in Korea. Korean Institute of Geoscience and Mineral Resources, Daejeon, Korea, 226p. Jeong, Y.S., Yu, J.H., Koh, S.M., and Heo, C.H. (2014) Spectroscopy of Skarn Minerals in Dangdu Pb-Zn Deposit and Assessment of Skarn Exploration Approaches Employing Portable Spectrometer. J. Miner. Soc. Korea, 27(3), 135-147 (in Korean with English abstract). Jeong, Y.S. Yu, J.H., Koh, S.M., Heo, C.H., and Lee, J.A. (2016) Spectral characteristics of minerals associated with skarn deposits: a case study of Weondong skarn deposit, South Korea. Geosciences Journal, 20(2), 167-182. Jung, G.B., Kim, W.I., Lee, J.S., Lee, J.S., Park, C.W., and Koh, M.H. (2005) Characteristics of heavy metal contamination in residual mine tailings near abandoned metalliferous mines in Korea. Korean Journal of Environmental Agriculture, 24(3), 222-231 (in Korean with English abstract). Kerr, A., Rafuse, H., Sparkes, G., Hinchey, J., and Sandeman, H. (2011) Visible/infrared spectroscopy (VIRS) as a research tool in economic geology: Background and pilot studies from Newfoundland and Labrador. Geological Survey, Report, 11, 145-166. Ki, S.K., Park, H.S., Jo, R.H., Choi, K.K., Yang, H., and Park, J.H. (2014) Distribution Correlation between Heavy Metals Contaminants and PAHs Concentrations of Soils in the Vicinity of Abandoned Mines. Korean Journal of Environmental Agriculture, 33(4), 239-244 (in Korean with English abstract). Kim, J.D. (2005) Assessment of Pollution Level and Contamination Status on Mine Tailings and Soil in the Vicinity of Disused Metal Mines in Kangwon Province. Journal of Korean Society of Environmental Engineers, 27(6), 626-634 (in Korean with English abstract). Kim. J.I., Yoon. J.G., Kim. N.Y., Lee, H.G., Ko, H.W., and Kim, T.S. (2015) Applicability of x-ray fluorescence analysis for Heavy Metal Analysis in soil. The Korean Society of Analytical Sciences, 215-216 (in Korean). Ko, K.H., Choi, W.J., Kwon, H.J., Kim, Y.M., and Lee. I.S. (2014). Mineralogical and geochemical study on ore minerals in Useok and Boksu mines, Hwanggangri area. 2014 The Geological Society of Korea, 244-244 (in Korean). Kokaly, R.F. and Clark, R.N. (1999) Spectroscopic determination of leaf biochemistry using band-depth analysis of absorption features and stepwise multiple linear regression. Remote sensing of environment, 67(3), 267-287. Kwon, H.I. (2014) Yearbook of MIRECO Statistics, Mine reclamation corporation, coal center, Seoul. Lee. H.G. and Choi, Y.S. (2016) Mapping copper and lead concentrations by incorporating advantageous aspects of ICP-AES and portable XRF analysis data. Joint Conference of the Geological Science & Technology of Korea, Busan, April 20-22, 163p. Lee, M.S. and Park, B.S. (1965). Instruction and geological survey of Hwanggangri area. Lee, S.E., Lee, J.S., and Chon, H.T. (2005) Environmental contamination and bioavailability assessment of heavy metals in the vicinity of the Dogok Au-Ag-Cu mine. Economic and Environmental Geology, 38(2), 135-142, (in Korean with English abstract). Liu, Y., Li, W., Wu, G., and Xu, X. (2011). Feasibility of estimating heavy metal contaminations in floodplain soils using laboratory-based hyperspectral data-A case study along Le’an River, China. Geo-spatial Information Science, 14(1), 10-16. Mine Reclamation Corporation. (2014) Reclamation of Dong-A Asbestos Mines District 1, 11p. Ministry of Environment. (2007) A Report of Soil Pollution Investigation abandon, 2007. Ministry of Environment. (2016) Soil Environment Conservation Act in Korea. Ministry of Environment and National Insitute of Environmnetal Research. (2014) Result of the soil quality monitoring network and the Soil Pollution Investigation, 2013. Ministry of Environment and National Insitute of Environmnetal Research. (2015) Heavy metal concentration on 74 site among 140 site of Abandoned Metal Mine in Gangweon and North Chungcheong Province. Na, E.S., Lee. Y.J. Ko, K.Y., Chung, D.Y., and Lee, K.S. (2013) Risk Assessment for Heavy Metals in Soil, Ground Water, Rice Grain nearby Abandoned Mine Areas. Korean Journal of Environmental Agriculture, Vol. 32, No. 4, 245-251 (in Korean with English abstract). National Institute of Environmental Research (2015) Environmental and Health Effects Survey of Residents around 2nd Phase Abandoned Metal Mines(II). Pandit, C.M., Filippelli, G.M., and Li, L. (2010) Estimation of heavy-metal contamination in soil using reflectance spectroscopy and partial least-squares regression. International Journal of Remote Sensing, 31(15), 4111-4123. Pontual, S,, Gamson, P., and Merry, N. (2012) Spectral interpretation field manual. Spectral analysis guides for Mineral Exploration, G-Mex Version 3.0. Ausspec International Pty. Ltd. Vol. 1. Rathod, P.H., Rossiter, D.G., Noomen, M.F., and Van der Meer, F.D. (2013) Proximal spectral sensing to monitor phytoremediation of metal-contaminated soils. International journal of phytoremediation, 15(5), 405-426. Ravet, N., Chouinard, Y., Magnan, J. F., Besner, S., Gauthier, M., and Armand, M. (2001). Electroactivity of natural and synthetic triphylite. Journal of Power Sources, 97, 503-507. Ren, H.Y., Zhuang, D.F., Singh, A.N., Pan, J.J., Qiu, D.S., and Shi, R.H. (2009) Estimation of As and Cu contamination in agricultural soils around a mining area by reflectance spectroscopy: A case study. Pedosphere, 19(6), 719-726. Rossel, R.A.V. and Behrens, T. (2010) Using data mining to model and interpret soil diffuse reflectance spectra. Geoderma, 158(1), 46-54. Shefsky, S. (1997) Comparing Field Portable X-Ray Fluorescence (XRF) to laboratory analysis of heavy metals in soil. In International Symposium of Field Screening Methods for Hazardous Wastes and Toxic Chemicals, Las Vegas, NV, 29-31 January. Sherman, D.M. and Waite, T.D. (1985) Electronic spectra of Fe3+ oxides and oxide hydroxides in the near IR to near UV. American Mineralogist, 70(11-12), 1262-1269. Shin, D. and Lee, I. (2003a) Evaluation of the volatilization and infiltration effects on the stable isotopic and mineralogical variations in the carbonate rocks adjacent to the Cretaceous Muamsa Granite, South Korea. Journal of Asian Earth Sciences, 22(3), 227-243. Shin, D. and Lee, I. (2003b) Carbonate-hosted talc deposits in the contact aureole of an igneous intrusion (Hwanggangri mineralized zone, South Korea): geochemistry, phase relationships, and stable isotope studies. Ore Geology Reviews, 22(1), 17-39. Thompson, A.J., Hauff, P.L., and Robitaille, A.J. (1999) Alteration mapping in exploration: application of short-wave infrared (SWIR) spectroscopy. SEG newsletter, 39, 16-27. Um, T.H., Kim, Y.T., Lee, K.G., Kim, Y.J., Kang, S.G., and Kim, J.H. (2002) Properties of heavy metal adsorption of clay minerals. Journal of the Korean Ceramic Society, 39(7), 663-668 (in Korean with English abstract). USEPA (2007) Method 6200: Field Portable X-ray Fluorescence Spectrometry for the Determination of Elemental Concentrations in Soil and Sediment. Available. online at: http://www.epa.gov/osw/hazard/testmethods/sw846/pdfs/6200.pdf (verified 30.04.13.).Usman, A. R. A. (2008) The relative adsorption selectivities of Pb, Cu, Zn, Cd and Ni by soils developed on shale in New Valley, Egypt. Geoderma, 144(1), 334-343.Weindorf, D.C., Paulette, L. and Man, T. (2013) In-situ assessment of metal contamination via portable X-ray fluorescence spectroscopy: Zlatna, Romania. Environmental pollution, 182, 92-100.Yun, S.K. (1974) The Mineralization In The Dandyang-Susan Area. YONSEI Nonchong, 11(1), 325-337 (in Korean).


This Article

e-submission

Archives