Upconversion nanoparticle-mediated photodynamic therapy induces autophagy and cholesterol efflux of macrophage-derived foam cells via ROS generation

Cell Death and Disease - Tập 8 Số 6 - Trang e2864-e2864
Xiaobo Han1, Hongxia X Li1, Xiufeng Zheng1, Hao Wang2, Xuesong S Li1, Jiayuan Kou1, Yinghong Zheng1, Zhongni N Liu1, Hong Li1, Jing Li3, Dou Dou4, You Wang5, Ye Tian6, Liming Yang1
1Department of Pathophysiology, Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin, China
2Department of Food Science and Engineering, College of Food Science, Northeast Agricultural University, Harbin, China
3Department of Electron Microscopic Center, Harbin Medical University, Harbin, China
4Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
5Materials Physics and Chemistry Department, Harbin Institute of Technology, Harbin, China
6Division of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

Tóm tắt

AbstractMacrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect. First, we found that PDT notably enhanced the cholesterol efflux and the induction of autophagy in both THP-1 and peritoneal macrophage-derived foam cells. The autophagy inhibitor 3-methyladenine and an ATG5 siRNA significantly attenuated PDT-induced autophagy, which subsequently suppressed the ABCA1-mediated cholesterol efflux. Furthermore, the reactive oxygen species (ROS) produced by PDT were responsible for the induction of autophagy, which could be blocked by the ROS inhibitor N-acetyl cysteine (NAC). NAC also reversed the PDT-induced suppression of p-mTOR and p-Akt. Therefore, our findings demonstrate that PDT promotes cholesterol efflux by inducing autophagy, and the autophagy was mediated in part through the ROS/PI3K/Akt/mTOR signaling pathway in THP-1 and peritoneal macrophage-derived foam cells.

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Tài liệu tham khảo

Wang F, Gao Q, Guo S, Cheng J, Sun X, Li Q et al. The sonodynamic effect of curcumin on THP-1 cell-derived ma crophages. BioMed Res Int 2013; 2013: 737264.

Sergin I, Razani B . Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis. Trends Endocrinol Metab 2014; 25: 225–234.

Patel KM, Strong A, Tohyama J, Jin X, Morales CR, Billheimer J et al. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res 2015; 116: 789–796.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372: 1489–1499.

Dolmans DE, Fukumura D, Jain RK . Photodynamic therapy for cancer. Nat Rev Cancer 2003; 3: 380–387.

Castano AP, Mroz P, Hamblin MR . Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 2006; 6: 535–545.

Tan J, Sun C, Xu K, Wang C, Guo J . Immobilization of ALA‐ZnII coordination polymer pro‐photosensitizers on magnetite colloidal supraparticles for target photodynamic therapy of bladder cancer. Small 2015; 11: 6338–6346.

Baldea I, Filip AG . Photodynamic therapy in melanoma–an update. J Physiol Pharmacol 2012; 63: 109–118.

Nowis D, Makowski M, Stokłosa T, Legat M, Issat T, Gołab J . Direct tumor damage mechanisms of photodynamic therapy. Acta Biochim Pol 2005; 52: 339–352.

Xiong L, Chen Z, Tian Q, Cao T, Xu C, Li F . High contrast upconversion luminescence targeted imaging in vivo using peptide-labeled nanophosphors. Anal Chem 2009; 81: 8687–8694.

Yang K, Xu H, Cheng L, Sun C, Wang J, Liu Z . In vitro and in vivo near-infrared photothermal therapy of cancer using polypyrrole organic nanoparticles. Adv Mater 2012; 24: 5586–5592.

Wang C, Cheng L, Liu Z . Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials 2011; 32: 1110–1120.

Garg AD, Dudek AM, Ferreira GB, Verfaillie T, Vandenabeele P, Krysko DV et al. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy 2013; 9: 1292–1307.

Zhu X, Wang H, Zheng L, Zhong Z, Li X, Zhao J et al. Upconversion nanoparticle-mediated photodynamic therapy induces THP-1 macrophage apoptosis via ROS bursts and activation of the mitochondrial caspase pathway. Int J Nanomedicine 2015; 10: 3719–3736.

Andrzejak M, Price M, Kessel DH . Apoptotic and autophagic responses to photodynamic therapy in 1c1c7 murine hepatoma cells. Autophagy 2011; 7: 979–984.

Hubbi ME, Semenza GL . An essential role for chaperone-mediated autophagy in cell cycle progression. Autophagy 2015; 11: 850–851.

Wang Y, Martins I, Ma Y, Kepp O, Galluzzi L, Kroemer G . Autophagy-dependent ATP release from dying cells via lysosomal exocytosis. Autophagy 2013; 9: 1624–1625.

Ouimet M, Marcel YL . Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arterioscler Thromb Vasc Biol 2012; 32: 575–581.

Wang L, Jiang Y, Song X, Guo C, Zhu F, Wang X et al. Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice. Cell Death Dis 2016; 7: e2055.

Liu K, Czaja MJ . Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ 2013; 20: 3–11.

Helal O, Berrougui H, Loued S, Khalil A . Extra-virgin olive oil consumption improves the capacity of HDL to mediate cholesterol efflux and increases ABCA1 and ABCG1 expression in human macrophages. Br J Nutr 2013; 109: 1844–1855.

Ji A, Wroblewski JM, Cai L, de Beer MC, Webb NR, van der Westhuyzen DR . Nascent HDL formation in hepatocytes and role of ABCA1, ABCG1, and SR-BI. J Lipid Res 2012; 53: 446–455.

Hou X, Hu Z, Xu H, Xu J, Zhang S, Zhong Y et al. Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway. Cardiovasc Diabetol 2014; 13: 78.

Kumar S, Guru SK, Pathania AS, Manda S, Kumar A, Bharate SB et al. Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J Cell Biochem 2015; 116: 985–997.

Ricchelli F, Šileikytė J, Bernardi P . Shedding light on the mitochondrial permeability transition. Biochim Biophys Acta 2011; 1807: 482–490.

Magi B, Ettorre A, Liberatori S, Bini L, Andreassi M, Frosali S et al. Selectivity of protein carbonylation in the apoptotic response to oxidative stress associated with photodynamic therapy: a cell biochemical and proteomic investigation. Cell Death Differ 2004; 11: 842–852.

Moore KJ, Sheedy FJ, Fisher EA . Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 2013; 13: 709–721.

Peng C, Li Y, Liang H, Cheng J, Li Q, Sun X et al. Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery of rabbits. J Photochem Photobiol B 2011; 102: 26–31.

Wei MF, Chen MW, Chen KC, Lou PJ, Lin SY, Hung SC et al. Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells. Autophagy 2014; 10: 1179–1192.

Kim J, Lim W, Kim S, Jeon S, Hui Z, Ni K et al. Photodynamic therapy (PDT) resistance by PARP1 regulation on PDT-induced apoptosis with autophagy in head and neck cancer cells. J Oral Pathol Med 2014; 43: 675–684.

Jiang P, Mizushima N . LC3-and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods 2015; 75: 13–18.

Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N et al. Autophagosomes form at ER-mitochondria contact sites. Nature 2013; 495: 389–393.

Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y . Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 1998; 23: 33–42.

Wang Y, Liu J, Tao Z, Wu P, Cheng W, Du Y et al. Exogenous HGF prevents cardiomyocytes from apoptosis after hypoxia via up-regulating cell autophagy. Cell Physiol Biochem 2016; 38: 2401–2413.

Shao B, Tang C, Sinha A, Mayer PS, Davenport GD, Brot N et al. Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase. Circ Res 2014; 114: 1733–1742.

Heinecke JW . Small HDL promotes cholesterol efflux by the ABCA pathway in macrophages implications for therapies targeted to HDL. Circ Res 2015; 116: 1101–1103.

Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J . The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 2014; 26: 2694–2701.

Ray PD, Huang BW, Tsuji Y . Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24: 981–990.

Hou J, Han ZP, Jing YY, Yang X, Zhang SS, Sun K et al. Autophagy prevents irradiation injury and maintains stemness through decreasing ROS generation in mesenchymal stem cells. Cell Death Dis 2013; 4: e844.

Wang H, Han R, Yang L, Shi J, Liu Z, Hu Y et al. Design and synthesis of core-shell-shell upconversion nanoparticles for NIR-induced drug release, photodynamic therapy, and cell imaging. ACS Appl Mater Interfaces 2016; 8: 4416–4423.

Wang H, Zhu X, Han R, Wang X, Ying LM, Wang Y et al. Near-infrared light activated photodynamic therapy of THP-1 macrophages based on core-shell structured upconversion nanoparticles. Micropor Mesopor Mater 2017; 239: 78–85.

Qiao X, Zhou J, Xiao J, Ye Wang, Sun L, Yan Chun . Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro. Nanoscale 2012; 4: 4611–4623.

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Cell Death and Disease

Tập 8 Số 6

e2864-e2864

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