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http://dx.doi.org/10.15324/kjcls.2020.52.3.245

Cathepsin B Is Implicated in Triglyceride (TG)-Induced Cell Death of Macrophage  

Jung, Byung Chul (Department of Nutritional Sciences and Toxicology, University of California)
Lim, Jaewon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
Publication Information
Korean Journal of Clinical Laboratory Science / v.52, no.3, 2020 , pp. 245-252 More about this Journal
Abstract
Macrophage cell death contributes to the formation of plaque, leading to the development of atherosclerosis. The accumulation of triglyceride (TG) is also associated with the pathogenesis of atherosclerosis. A previous study reported that TG induces the cell death of macrophages. This study examined whether the cytoplasmic release of cathepsin B from lysosome is associated with the TG-induced cell death of macrophage. The release of cathepsin B was increased in the TG-treated THP-1 macrophages, but the TG treatment did not affect cathepsin B expression. Furthermore, the inhibition of cathepsin B by its inhibitor, CA-074 Me, partially inhibited the TG-induced cell death of macrophage. TG-triggered macrophage cell death is mediated by the activation of caspase-1, -2, and apoptotic caspases. Therefore, this study investigated whether cathepsin B is implicated in the activation of these caspases. The inhibition of cathepsin B blocked the activation of caspase-7, -8, and -1 but did not affect the activity of caspase-3, -9, and -2. Overall, these results suggest that TG-induced cytoplasmic cathepsin B causes THP-1 macrophage cell death by activating caspase-1, leading to subsequent activation of the extrinsic apoptotic pathway.
Keywords
Caspase-1; Cathepsin B; Cell death; THP-1 macrophage; Triglyceride;
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1 Chevriaux A, Pilot T, Derangere V, Simonin H, Martine P, Chalmin F, et al. Cathepsin B is required for NLRP3 inflammasome activation in macrophages, through NLRP3 interaction. Front Cell Dev Biol. 2020;8:167. https://doi.org/10.3389/fcell.2020.00167   DOI
2 Aronis A, Madar Z, Tirosh O. Lipotoxic effects of triacylglycerols in j774.2 macrophages. Nutrition. 2008;24:167-176. https://doi.org/10.1016/j.nut.2007.10.017   DOI
3 Tsuchiya S, Kobayash Y, Goto Y, Okumura H, Nakae S, Konno T, et al. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982;42:1530-1536.
4 Auwerx J. The human leukemia cell line, THP-1: A multifacetted model for the study of monocyte-macrophage differentiation. Experentia. 1991;47:22-31. https://do.org/10.1007/BF02041244   DOI
5 Dimauro I, Pearson T, Caporossi D, Jackson MJ. A simple protocol for the subcellular fractionation of skeletal muscle cells and tissue. BMC Res Notes. 2012;5:513. https://doi.org/10.1186/1756-0500-5-513   DOI
6 Jo HS, Kim DS, Ahn EH, Kim DW, Shin MJ, Cho SB, et al. Protective effects of TAT-NQO1 against oxidative stress-induced HT-22 cell damage, and ischemic injury in animals. BMB Rep. 2016;49:617-622.   DOI
7 Joo D, Woo JS, Cho KH, Han SH, Min TS, Yang DC, et al. Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells. BMB Rep. 2016;49:220-225. https://doi.org/10.5483/bmbrep.2016.49.11.117   DOI
8 Guicciardi ME, Leist M, Gores GJ. Lysosomes in cell death. Oncogene. 2004;23:2881-2890. https://doi.org/10.1038/sj.onc.1207512   DOI
9 Bruchard M, Mignot G, Derangere V, Chalmin F, Chevriaux A, Vegran F, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the NLRP3 inflammasome and promotes tumor growth. Nat Med. 2013;19: 57-64. https://doi.org/10.1038/nm.2999   DOI
10 Han SH, Nicholls SJ, Sakuma I, Zhao D, Koh KK. Hypertriglyceridemia and cardiovascular diseases: Revisited. Korean Circ J. 2016;46:135-144. https://doi.org/10.4070/kcj.2016.46.2.135   DOI
11 Wuopio J, Hilden J, Bring C, Kastrup J, Sajadieh A, Jensen GB, et al. Cathepsin B and s as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: A claricor trial sub-study. Atherosclerosis. 2018;278:97-102. https://doi.org/10.1016/j.atherosclerosis.2018.09.006   DOI
12 Tabas I. Macrophage apoptosis in atherosclerosis: Consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal. 2009;11:2333-2339. https://doi.org/10.1089/ars.2009.2469   DOI
13 Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: A dynamic balance. Nat Rev Immunol. 2013;13:709-721. https://doi.org/10.1186/s12889-019-7439-0   DOI
14 Premzl A, Turk V, Kos J. Intracellular proteolytic activity of cathepsin B is associated with capillary-like tube formation by endothelial cells in vitro. J Cell Biochem. 2006;97:1230-1240. https://doi.org/10.1002/jcb.20720   DOI
15 Ndrepepa G. Atherosclerosis and ischaemic heart disease: Here to stay or gone tomorrow. Indian J Med Res. 2017;146:293-297. https://doi.org/10.4103/ijmr.IJMR_1668_17
16 Kim H, Kim S, Han S, Rane PP, Fox KM, Qian Y, et al. Prevalence and incidence of atherosclerotic cardiovascular disease and its risk factors in korea: A nationwide population-based study. BMC Public Health. 2019;19:1112. http://doi.org/10.1186/s12889-019-7439-0   DOI
17 Rader DJ, Pure E. Lipoproteins, macrophage function, and atherosclerosis: Beyond the foam cell? Cell Metab. 2005;1:223-230. https://doi.org/10.1016/j.cmet.2005.03.005   DOI
18 Tabas I. Apoptosis and plaque destabilization in atherosclerosis: The role of macrophage apoptosis induced by cholesterol. Cell Death Differ. 2004;(11 Suppl 1):12-16. https://doi.org/10.1038/sj.cdd.4401444
19 Son SJ, Rhee KJ, Lim J, Kim TU, Kim TJ, Kim YS. Triglyceride-induced macrophage cell death is triggered by caspase-1. Biol Pharm Bull. 2013;36:108-113. https://doi.org/10.1248/bpb.b12-00571   DOI
20 Lim J, Kim HK, Kim SH, Rhee KJ, Kim YS. Caspase-2 mediates triglyceride (TG)-induced macrophage cell death. BMB Rep. 2017;50:510-515. https://doi.org/10.5483/bmbrep.2017.50.10.106   DOI
21 Perisic Nanut M, Sabotic J, Jewett A, Kos J. Cysteine cathepsins as regulators of the cytotoxicity of NK and T cells. Front Immunol. 2014;5:616. https://doi.org/10.3389/fimmu.2014.00616
22 Li W, Yuan XM. Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis. Ann N Y Acad Sci. 2004;1030:427-433. https://doi.org/10.1196/annals.1329.053   DOI
23 Liu CL, Guo J, Zhang X, Sukhova GK, Libby P, Shi GP. Cysteine protease cathepsins in cardiovascular disease: From basic research to clinical trials. Nat Rev Cardiol. 2018;15:351-370. https://doi.org/10.1038/s41569-018-0002-3   DOI
24 Chen J, Tung CH, Mahmood U, Ntziachristos V, Gyurko R, Fishman MC, et al. In vivo imaging of proteolytic activity in atherosclerosis. Circulation. 2002;105:2766-2771. https://doi.org/10.1161/01.cir.0000017860.20619.23   DOI
25 Zhao CF, Herrington DM. The function of cathepsins B, D, and X in atherosclerosis. Am J Cardiovasc Dis. 2016;6:163-170.
26 Hentze H, Lin XY, Choi MS, Porter AG. Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1-independent necrosis triggered by the microbial toxin nigericin. Cell Death Differ. 2003;10:956-968. https://doi.org/10.1038/sj.cdd.4401264   DOI
27 Lim J, Kim YS, Kim SH, Cho Y, Lee MH, Jung BC. et al. Triglyceride enhances susceptibility to TNF-$\alpha$-induced cell death in THP-1 cells. Genes & Genomics. 2013;36:87-93. https://doi.org/10.1007/s13258-013-0144-y   DOI
28 Foghsgaard L, Wissing D, Mauch D, Lademann U, Bastholm L, Boes M, et al. Cathepsin B acts as a dominant execution protease in tumor cell apoptosis induced by tumor necrosis factor. J Cell Biol. 2001;153:999-1010. https://doi.org/10.1083/jcb.153.5.999   DOI