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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

Author(s): Yuan Yang, Jin Huang, Jianzhong Li, Huansheng Yang* and Yulong Yin

Volume 20, Issue 4, 2020

Page: [307 - 317] Pages: 11

DOI: 10.2174/1566524019666191024110443

Price: $65

Abstract

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated.

Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase.

Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes.

Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

Keywords: Butyrate, p38 MAPK, apoptosis, autophagy, V-ATPase, lysosome.

[1]
Bach Knudsen KE, Serena A, Canibe N, Juntunen KS. New insight into butyrate metabolism. Proc Nutr Soc 2003; 62(1): 81-6.
[http://dx.doi.org/10.1079/PNS2002212] [PMID: 12740062]
[2]
Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet 1980; 2(8197): 712-5.
[http://dx.doi.org/10.1016/S0140-6736(80)91934-0] [PMID: 6106826]
[3]
Kien CL, Blauwiekel R, Bunn JY, Jetton TL, Frankel WL, Holst JJ. Cecal infusion of butyrate increases intestinal cell proliferation in piglets. J Nutr 2007; 137(4): 916-22.
[http://dx.doi.org/10.1093/jn/137.4.916] [PMID: 17374654]
[4]
Peng L, He Z, Chen W, Holzman IR, Lin J. Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier. Pediatr Res 2007; 61(1): 37-41.
[http://dx.doi.org/10.1203/01.pdr.0000250014.92242.f3] [PMID: 17211138]
[5]
Claus R, Lösel D, Lacorn M, Mentschel J, Schenkel H. Effects of butyrate on apoptosis in the pig colon and its consequences for skatole formation and tissue accumulation. J Anim Sci 2003; 81(1): 239-48.
[http://dx.doi.org/10.2527/2003.811239x] [PMID: 12597395]
[6]
Mentschel J, Claus R. Increased butyrate formation in the pig colon by feeding raw potato starch leads to a reduction of colonocyte apoptosis and a shift to the stem cell compartment. Metabolism 2003; 52(11): 1400-5.
[http://dx.doi.org/10.1016/S0026-0495(03)00318-4] [PMID: 14624397]
[7]
Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr 2009; 139(9): 1619-25.
[http://dx.doi.org/10.3945/jn.109.104638] [PMID: 19625695]
[8]
Nofrarías M, Martínez-Puig D, Pujols J, Majó N, Pérez JF. Long-term intake of resistant starch improves colonic mucosal integrity and reduces gut apoptosis and blood immune cells. Nutrition 2007; 23(11-12): 861-70.
[http://dx.doi.org/10.1016/j.nut.2007.08.016] [PMID: 17936196]
[9]
Kotunia A, Woliński J, Laubitz D, et al. Effect of sodium butyrate on the small intestine development in neonatal piglets fed [correction of feed] by artificial sow. J Physiol Pharmacol 2004; 55(Suppl. 2): 59-68.
[10]
Lu JJ, Zou XT, Wang YM. Effects of sodium butyrate on the growth performance, intestinal microflora and morphology of weanling pigs. J Anim Feed Sci 2008; 17(4): 568-78.
[http://dx.doi.org/10.22358/jafs/66685/2008]
[11]
Claus R, Günthner D, Letzguss H. Effects of feeding fat-coated butyrate on mucosal morphology and function in the small intestine of the pig. J Anim Physiol Anim Nutr (Berl) 2007; 91(7-8): 312-8.
[http://dx.doi.org/10.1111/j.1439-0396.2006.00655.x] [PMID: 17615002]
[12]
Le Gall M, Gallois M, Sève B, et al. Comparative effect of orally administered sodium butyrate before or after weaning on growth and several indices of gastrointestinal biology of piglets. Br J Nutr 2009; 102(9): 1285-96.
[http://dx.doi.org/10.1017/S0007114509990213] [PMID: 19480733]
[13]
Yan H, Ajuwon KM. Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS One 2017; 12(6)e0179586
[http://dx.doi.org/10.1371/journal.pone.0179586] [PMID: 28654658]
[14]
Qiu Y, Ma X, Yang X, Wang L, Jiang Z. Effect of sodium butyrate on cell proliferation and cell cycle in porcine intestinal epithelial (IPEC-J2) cells. In Vitro Cell Dev Biol Anim 2017; 53(4): 304-11.
[http://dx.doi.org/10.1007/s11626-016-0119-9] [PMID: 28127702]
[15]
Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 1988; 29(8): 1035-41.
[http://dx.doi.org/10.1136/gut.29.8.1035] [PMID: 3410329]
[16]
Hinnebusch BF, Siddique A, Henderson JW, et al. Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor. Am J Physiol Gastrointest Liver Physiol 2004; 286(1): G23-30.
[http://dx.doi.org/10.1152/ajpgi.00203.2003] [PMID: 12919939]
[17]
Diesing AK, Nossol C, Panther P, et al. Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2. Toxicol Lett 2011; 200(1-2): 8-18.
[http://dx.doi.org/10.1016/j.toxlet.2010.10.006] [PMID: 20937367]
[18]
Cury-Boaventura MF, Curi R. Regulation of reactive oxygen species (ROS) production by C18 fatty acids in Jurkat and Raji cells. Clin Sci (Lond) 2005; 108(3): 245-53.
[http://dx.doi.org/10.1042/CS20040281] [PMID: 15563273]
[19]
Liu F, Wang L, Fu JL, et al. Analysis of non-sumoylated and sumoylated isoforms of Pax-6, the master regulator for eye and brain development in ocular cell lines. Curr Mol Med 2018; 18(8): 566-73.
[http://dx.doi.org/10.2174/1566524019666190111153310] [PMID: 30636604]
[20]
Hendzel MJ, Wei Y, Mancini MA, et al. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 1997; 106(6): 348-60.
[http://dx.doi.org/10.1007/s004120050256] [PMID: 9362543]
[21]
Van Herreweghe F, Festjens N, Declercq W, Vandenabeele P. Tumor necrosis factor-mediated cell death: to break or to burst, that’s the question. Cell Mol Life Sci 2010; 67(10): 1567-79.
[http://dx.doi.org/10.1007/s00018-010-0283-0] [PMID: 20198502]
[22]
González-Flores D, Rodríguez AB, Pariente JA. TNFα-induced apoptosis in human myeloid cell lines HL-60 and K562 is dependent of intracellular ROS generation. Mol Cell Biochem 2014; 390(1-2): 281-7.
[http://dx.doi.org/10.1007/s11010-014-1979-5] [PMID: 24488173]
[23]
Shen HM, Pervaiz S. TNF receptor superfamily-induced cell death: redox-dependent execution. FASEB J 2006; 20(10): 1589-98.
[http://dx.doi.org/10.1096/fj.05-5603rev] [PMID: 16873882]
[24]
Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011; 469(7330): 323-35.
[http://dx.doi.org/10.1038/nature09782] [PMID: 21248839]
[25]
Tang Y, Li J, Li F, et al. Autophagy protects intestinal epithelial cells against deoxynivalenol toxicity by alleviating oxidative stress via IKK signaling pathway. Free Radic Biol Med 2015; (89): 944-51.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.09.012]
[26]
Chen JW, Murphy TL, Willingham MC, Pastan I, August JT. Identification of two lysosomal membrane glycoproteins. J Cell Biol 1985; 101(1): 85-95.
[http://dx.doi.org/10.1083/jcb.101.1.85] [PMID: 2409098]
[27]
Barone MV, Crozat A, Tabaee A, Philipson L, Ron D. CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest. Genes Dev 1994; 8(4): 453-64.
[http://dx.doi.org/10.1101/gad.8.4.453] [PMID: 8125258]
[28]
Dzierzewicz Z, Orchel A, Weglarz L, Latocha M, Wilczok T. Changes in the cellular behaviour of human colonic cell line Caco-2 in response to butyrate treatment. Acta Biochim Pol 2002; 49(1): 211-20.
[PMID: 12136943]
[29]
Verma SP, Agarwal A, Das P. Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146. In Vitro Cell Dev Biol Anim 2018; 54(4): 295-303.
[http://dx.doi.org/10.1007/s11626-018-0239-5] [PMID: 29556894]
[30]
Schwab M, Reynders V, Steinhilber D, Stein J. Combined treatment of Caco-2 cells with butyrate and mesalazine inhibits cell proliferation and reduces Survivin protein level. Cancer Lett 2009; 273(1): 98-106.
[http://dx.doi.org/10.1016/j.canlet.2008.07.027] [PMID: 18774638]
[31]
Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016; 1863(12): 2977-92.
[http://dx.doi.org/10.1016/j.bbamcr.2016.09.012] [PMID: 27646922]
[32]
Zhan J, He J, Zhou Y, et al. Crosstalk between the autophagy-lysosome pathway and the ubiquitin-proteasome pathway in retinal pigment epithelial cells. Curr Mol Med 2016; 16(5): 487-95.
[http://dx.doi.org/10.2174/1566524016666160429121606] [PMID: 27132793]
[33]
Kondo Y, Kondo S. Autophagy and cancer therapy. Autophagy 2006; 2(2): 85-90.
[http://dx.doi.org/10.4161/auto.2.2.2463] [PMID: 16874083]
[34]
Munson MJ, Ganley IG. MTOR, PIK3C3, and autophagy: Signaling the beginning from the end. Autophagy 2015; 11(12): 2375-6.
[http://dx.doi.org/10.1080/15548627.2015.1106668] [PMID: 26565689]
[35]
Serrano-Puebla A, Boya P. Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease. Ann N Y Acad Sci 2016; 1371(1): 30-44.
[http://dx.doi.org/10.1111/nyas.12966] [PMID: 26599521]
[36]
Colacurcio DJ, Nixon RA. Disorders of lysosomal acidification-The emerging role of v-ATPase in aging and neurodegenerative disease. Ageing Res Rev 2016; (32): 75-88.
[http://dx.doi.org/10.1016/j.arr.2016.05.004]
[37]
Xiao T, Wu S, Yan C, et al. Butyrate upregulates the TLR4 expression and the phosphorylation of MAPKs and NK-κB in colon cancer cell in vitro. Oncol Lett 2018; 16(4): 4439-47.
[PMID: 30214578]
[38]
Han A, Bennett N, Ahmed B, Whelan J, Donohoe DR. Butyrate decreases its own oxidation in colorectal cancer cells through inhibition of histone deacetylases. Oncotarget 2018; 9(43): 27280-92.
[http://dx.doi.org/10.18632/oncotarget.25546] [PMID: 29930765]
[39]
McHenry P, Wang WL, Devitt E, et al. Iejimalides A and B inhibit lysosomal vacuolar H+-ATPase (V-ATPase) activity and induce S-phase arrest and apoptosis in MCF-7 cells. J Cell Biochem 2010; 109(4): 634-42.
[PMID: 20039309]
[40]
Mei F, You J, Liu B, et al. LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity. Tumour Biol 2015; 36(4): 2831-44.
[http://dx.doi.org/10.1007/s13277-014-2910-0] [PMID: 25501280]
[41]
Aasebø E, Bartaula-Brevik S, Hernandez-Valladares M, Bruserud Ø. Vacuolar ATPase as a possible therapeutic target in human acute myeloid leukemia. Expert Rev Hematol 2018; 11(1): 13-24.
[http://dx.doi.org/10.1080/17474086.2018.1407239] [PMID: 29168399]
[42]
Jung YS, Jun S, Kim MJ, et al. TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling. Nat Cell Biol 2018; 20(12): 1421-33.
[http://dx.doi.org/10.1038/s41556-018-0219-8] [PMID: 30374053]
[43]
Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell 2012; 48(4): 612-26.
[http://dx.doi.org/10.1016/j.molcel.2012.08.033] [PMID: 23063526]
[44]
Li Q, Ding C, Meng T, et al. Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner. J Pharmacol Sci 2017; 135(4): 148-55.
[http://dx.doi.org/10.1016/j.jphs.2017.11.004] [PMID: 29233468]

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