DOI QR코드

DOI QR Code

Effects of gamma-aminobutyric acid and piperine on gene regulation in pig kidney epithelial cell lines

  • Shin, Juhyun (Department of Stem Cell and Regenerative Biotechnology, KIT, Konkuk University) ;
  • Lee, Yoon-Mi (Department of Stem Cell and Regenerative Biotechnology, KIT, Konkuk University) ;
  • Oh, Jeongheon (Department of Stem Cell and Regenerative Biotechnology, KIT, Konkuk University) ;
  • Jung, Seunghwa (Department of Stem Cell and Regenerative Biotechnology, KIT, Konkuk University) ;
  • Oh, Jae-Wook (Department of Stem Cell and Regenerative Biotechnology, KIT, Konkuk University)
  • Received : 2019.09.25
  • Accepted : 2019.12.14
  • Published : 2020.09.01

Abstract

Objective: Gamma-aminobutyric acid (GABA) and piperine (PIP) are both nutritional supplements with potential use in animal diets. The purpose of this study is to investigate the effect of GABA and/or PIP treatment on the gene expression pattern of a pig kidney epithelial cell line. Methods: LLCPK1 cells were treated with GABA, PIP, or both, and then the gene expression pattern was analyzed using microarray. Gene ontology analysis was done using GeneOntology (Geneontology.org), and validation was performed using quantitative real-time polymerase chain reaction. Results: Gene ontology enrichment analysis was used to identify key pathway(s) of genes whose expression levels were regulated by these treatments. Microarray results showed that GABA had a positive effect on the transcription of genes related to regulation of erythrocyte differentiation and that GABA and PIP in combination had a synergistic effect on genes related to immune systems and processes. Furthermore, we found that effects of GABA and/or PIP on these selected genes were controlled by JNK/p38 MAPK pathway. Conclusion: These results can improve our understanding of mechanisms involved in the effect of GABA and/or PIP treatment on pig kidney epithelial cells. They can also help us evaluate their potential as a clinical diagnosis and treatment.

Keywords

References

  1. Bowery NG, Smart TG. GABA and glycine as neurotransmitters: a brief history. Br J Pharmacol 2006;147(Suppl 1):S109-19. https://doi.org/10.1038/sj.bjp.0706443
  2. Wong CGT, Bottiglieri T, Snead OC, 3rd. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol 2003;54(Suppl 6):S3-12. https://doi.org/10.1002/ana.10696
  3. Hashimoto T. GABA receptor chloride ion channel. Nihon Rinsho 1998;56:1824-9.
  4. Bettler B, Kaupmann K, Bowery N. GABAB receptors: drugs meet clones. Curr Opin Neurobiol 1998;8:345-50. https://doi.org/10.1016/S0959-4388(98)80059-7
  5. Roberts E, Frankel S, Harman PJ. Amino acids of nervous tissue. Proc Soc Exp Biol Med 1950;74:383-7. https://doi.org/10.3181/00379727-74-17916
  6. Takano K, Yatabe MS, Abe A, et al. Characteristic expressions of GABA receptors and GABA producing/transporting molecules in rat kidney. PLoS One 2014;9:e105835. https://doi.org/10.1371/journal.pone.0105835
  7. Govindarajan VS. Pepper - chemistry, technology, and quality evaluation. CRC Crit Rev Food Sci Nutr 1977;9:115-225. https://doi.org/10.1080/10408397709527233
  8. Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res 2013;27:1121-30. https://doi.org/10.1002/ptr.4972
  9. Abou-Elkhair R, Ahmed HA, Selim S. Effects of black pepper (Piper nigrum), turmeric powder (Curcuma longa) and coriander seeds (Coriandrum sativum) and their combinations as feed additives on growth performance, carcass traits, some blood parameters and humoral immune response of broiler chickens. Asian-Australas J Anim Sci 2014;27:847-54. https://doi.org/10.5713/ajas.2013.13644
  10. Khom S, Strommer B, Schoffmann A, et al. GABAA receptor modulation by piperine and a non-TRPV1 activating derivative. Biochem Pharmacol 2013;85:1827-36. https://doi.org/10.1016/j.bcp.2013.04.017
  11. Lee YM, Choi JH, Min WK, Han JK, Oh JW. Induction of functional erythropoietin and erythropoietin receptor gene expression by gamma-aminobutyric acid and piperine in kidney epithelial cells. Life Sci 2018;215:207-15. https://doi.org/10.1016/j.lfs.2018.11.024
  12. Nairz M, Sonnweber T, Schroll A, Theurl I, Weiss G. The pleiotropic effects of erythropoietin in infection and inflammation. Microbes Infect 2012;14:238-46. https://doi.org/10.1016/j.micinf.2011.10.005
  13. Babicki S, Arndt D, Marcu A, et al. Heatmapper: web-enabled heat mapping for all. Nucleic Acids Res 2016;44:W147-53. https://doi.org/10.1093/nar/gkw419
  14. Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res 2019;47:D419-26. https://doi.org/10.1093/nar/gky1038
  15. Thomas PD, Campbell MJ, Kejariwal A, et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res 2003;13:2129-41. https://doi.org/10.1101/gr.772403
  16. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001;29:e45. https://doi.org/10.1093/nar/29.9.e45
  17. Stalteri MA, Harrison AP. Interpretation of multiple probe sets mapping to the same gene in Affymetrix GeneChips. BMC Bioinformatics 2007;8:13. https://doi.org/10.1186/1471-2105-8-13
  18. Solas M, Puerta E, Ramirez MJ. Treatment options in alzheimer's disease: the GABA story. Curr Pharm Des 2015;21:4960-71. https://doi.org/10.2174/1381612821666150914121149
  19. Wang S, Zhang L, Liu C, Lu WY. Protective roles of hepatic GABA signaling in liver injury. Int J Physiol Pathophysiol Pharmacol 2017;9:153.
  20. Han D, Kim HY, Lee HJ, Shim I, Hahm DH. Wound healing activity of gamma-aminobutyric Acid (GABA) in rats. J Microbiol Biotechnol 2007;17:1661-9.
  21. Sasaki S, Yokozawa T, Cho EJ, Oowada S, Kim M. Protective role of gamma-aminobutyric acid against chronic renal failure in rats. J Pharm Pharmacol 2006;58:1515-25. https://doi.org/10.1211/jpp.58.11.0013
  22. Wang DM, Wang C, Liu HY, Liu JX, Ferguson JD. Effects of rumen-protected gamma-aminobutyric acid on feed intake, lactation performance, and antioxidative status in early lactating dairy cows. J Dairy Sci 2013;96:3222-7. https://doi.org/10.3168/jds.2012-6285
  23. Mamuad LL, Kim SH, Ku MJ, Lee SS. Effect of gamma-aminobutyric acid producing bacteria on in vitro rumen fermentation, growth performance, and meat quality of Hanwoo steers. Asian-Australas J Anim Sci 2020;33:1087-95. https://doi.org/10.5713/ajas.19.0785
  24. Li X, Hao J, Liu X, et al. Effect of the treatment by slightly acidic electrolyzed water on the accumulation of gamma-aminobutyric acid in germinated brown millet. Food Chem 2015;186:249-55. https://doi.org/10.1016/j.foodchem.2015.03.004
  25. Windisch W, Schedle K, Plitzner C, Kroismayr A. Use of phytogenic products as feed additives for swine and poultry. J Anim Sci 2008;86(Issue suppl_14):E140-8. https://doi.org/10.2527/jas.2007-0459
  26. Giannenas I, Papaneophytou CP, Tsalie E, et al. Dietary supplementation of benzoic acid and essential oil compounds affects buffering capacity of the feeds, performance of Turkey Poults and their antioxidant status, pH in the digestive tract, intestinal microbiota and morphology. Asian-Australas J Anim Sci 2014;27:225-36. https://doi.org/10.5713/ajas.2013.13376
  27. da Silva Cardoso V, Vermelho AB, Ribeiro de Lima CA, et al. Antigenotoxic effect of piperine in broiler chickens intoxicated with Aflatoxin B1. Toxins (Basel) 2016;8:316. https://doi.org/10.3390/toxins8110316
  28. Cardoso VD, de Lima CAR, de Lima MEF, Dorneles LEG, Danelli MDM. Piperine as a phytogenic additive in broiler diets. Pesquisa Agropecuaria Brasileira 2012;47:489-96. https://doi.org/10.1590/S0100-204X2012000400003
  29. Seder CW, Hartojo W, Lin L, et al. Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma. Neoplasia 2009;11:388-96. https://doi.org/10.1593/neo.81582
  30. Huang Z, Richmond TD, Muntean AG, Barber DL, Weiss MJ, Crispino JD. STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice. J Clin Invest 2007;117:3890-9. https://doi.org/10.1172/JCI33010
  31. Choi SM, Choi KO, Park YK, Cho H, Yang EG, Park H. Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination and asparagine hydroxylation of hypoxia-inducible factor-1alpha, leading to expression of vascular endothelial growth factor and erythropoietin in normoxic cells. J Biol Chem 2006;281:34056-63. https://doi.org/10.1074/jbc.M603913200
  32. Dale DG, Macdonald MA, Moxley JE. Hemoglobin levels of piglets at birth and at 21 days and their relation to weight at 154 days of age. Can J Comp Med Vet Sci 1961;25:193-7.
  33. Dame C, Kirschner KM, Bartz KV, Wallach T, Hussels CS, Scholz H. Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene. Blood 2006;107:4282-90. https://doi.org/10.1182/blood-2005-07-2889
  34. Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 2013;27:41-53. https://doi.org/10.1016/j.blre.2012.12.003
  35. Li Q, Yan J, Mao AP, et al. Tripartite motif 8 (TRIM8) modulates TNFalpha- and IL-1beta-triggered NF-kappaB activation by targeting TAK1 for K63-linked polyubiquitination. Proc Natl Acad Sci USA 2011;108:19341-6. https://doi.org/10.1073/pnas.1110946108
  36. Wan YY. GATA3: a master of many trades in immune regulation. Trends Immunol 2014;35:233-42. https://doi.org/10.1016/j.it.2014.04.002
  37. Akram KM, Moyo NA, Leeming GH, et al. An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection. Mucosal Immunol 2018;11:71-81. https://doi.org/10.1038/mi.2017.45
  38. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015;7:a016303. https://doi.org/10.1101/cshperspect.a016303
  39. Zorova LD, Popkov VA, Plotnikov EY, et al. Mitochondrial membrane potential. Anal Biochem 2018;552:50-9. https://doi.org/10.1016/j.ab.2017.07.009