Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein

Park,Sin-Hye; Shin,Min  Jae; Kim,Dae  Won; Park,Jinseu; Choi,Soo  Young; Kang,Young-Hee

doi:10.3892/ijmm.2015.2444

Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein

Authors:
- Sin-Hye Park
- Min Jae Shin
- Dae Won Kim
- Jinseu Park
- Soo Young Choi
- Young-Hee Kang
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Affiliations: Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 200-702, Republic of Korea, Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 200-702, Republic of Korea
Published online on: December 23, 2015 https://doi.org/10.3892/ijmm.2015.2444
Pages: 387-397
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has previously been suggested that reactive oxygen species (ROS) are involved in the pathogenesis of chronic inflammatory diseases, which entails the initial activation of pro-inflammatory cytokines to facilitate leukocyte transmigration. The present study investigated whether intracellular superoxide dismutase (SOD) suppressed monocyte endothelial trafficking and transmigration. Human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes were activated by the cytokine tumor necrosis factor-α (TNF-α) in the absence and presence of cell-permeable transactivator of transcription (Tat)-SOD protein. External stimulation with SOD was conducted using endothelial cells and monocytes. Purified cell-permeable Tat-SOD, but not non-targeted SOD, at 1-3 µM was transduced into endothelial cells in a time‑ and dose-dependent manner. Non-toxic Tat-SOD at ≤0.5 µM, but not 1 µM SOD, blocked the monocyte-endothelium interactions by inhibiting the TNF-α-induced stimulation of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs and integrin β1 in THP-1 cells. Endothelial VCAM-1 induction by TNF-α was responsible for superoxide anion production being quenched by N-acetyl-cysteine and Tat-SOD. SOD treatment markedly inhibited superoxide anion production induced by TNF-α, but no inhibition of endothelial transmigration was noted. Tat-SOD prevented transendothelial monocyte migration by firmly localizing occludin-1, platelet/endothelial cell adhesion molecule‑1 (PECAM-1) and vascular endothelial‑cadherin present in paracellular junctions and inhibiting endothelial induction and activation of matrix-degrading membrane type-1 (MT-1) matrix metalloproteinase (MMP), MMP-2 and MMP-9. By contrast, treatment with 1 µM SOD did not have such effects. Furthermore, transduced Tat-SOD hindered nuclear transactivation of nuclear factor-κB (NF-κB), modulating the induction of paracellular junction proteins and matrix‑degrading MMP in TNF-α‑stimulated HUVECs. Transduced Tat-SOD, but not external SOD, impeded cytokine-induced endothelial adhesion and the transmigration of monocytes. Thus, we suggest that transduced Tat-SOD qualifies as an atheroprotective agent against oxidation-driven and inflammation-associated atherosclerosis.

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1	Magenta A, Greco S, Gaetano C and Martelli F: Oxidative stress and microRNAs in vascular diseases. Int J Mol Sci. 14:17319–17346. 2013. View Article : Google Scholar : PubMed/NCBI
2	Wen YD, Wang H, Kho SH, Rinkiko S, Sheng X, Shen HM and Zhu YZ: Hydrogen sulfide protects HUVECs against hydrogen peroxide induced mitochondrial dysfunction and oxidative stress. PLoS One. 8:e531472013. View Article : Google Scholar : PubMed/NCBI
3	Badimon L, Storey RF and Vilahur G: Update on lipids, inflammation and atherothrombosis. Thromb Haemost. 105(Suppl 1): S34–S42. 2011. View Article : Google Scholar : PubMed/NCBI
4	Rocha VZ and Libby P: Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol. 6:399–409. 2009. View Article : Google Scholar : PubMed/NCBI
5	Sprague AH and Khalil RA: Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 78:539–552. 2009. View Article : Google Scholar : PubMed/NCBI
6	Immenschuh S and Schröder H: Heme oxygenase-1 and cardiovascular disease. Histol Histopathol. 21:679–685. 2006.PubMed/NCBI
7	Armstrong AW, Voyles SV, Armstrong EJ, Fuller EN and Rutledge JC: Angiogenesis and oxidative stress: common mechanisms linking psoriasis with atherosclerosis. J Dermatol Sci. 63:1–9. 2011. View Article : Google Scholar : PubMed/NCBI
8	Chen YH, Lin SJ, Chen YL, Liu PL and Chen JW: Anti-inflammatory effects of different drugs/agents with antioxidant property on endothelial expression of adhesion molecules. Cardiovasc Hematol Disord Drug Targets. 6:279–304. 2006. View Article : Google Scholar
9	Fukai T and Ushio-Fukai M: Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 15:1583–1606. 2011. View Article : Google Scholar : PubMed/NCBI
10	Seguí J, Gironella M, Sans M, Granell S, Gil F, Gimeno M, Coronel P, Piqué JM and Panés J: Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine. J Leukoc Biol. 76:537–544. 2004. View Article : Google Scholar : PubMed/NCBI
11	Lubrano V and Balzan S: LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free Radic Res. 48:841–848. 2014. View Article : Google Scholar : PubMed/NCBI
12	Shuvaev VV, Han J, Tliba S, Arguiri E, Christofidou-Solomidou M, Ramirez SH, Dykstra H, Persidsky Y, Atochin DN, Huang PL and Muzykantov VR: Anti-inflammatory effect of targeted delivery of SOD to endothelium: mechanism, synergism with NO donors and protective effects in vitro and in vivo. PLoS One. 8:e770022013. View Article : Google Scholar : PubMed/NCBI
13	Zahid M and Robbins PD: Protein transduction domains: applications for molecular medicine. Curr Gene Ther. 12:374–380. 2012. View Article : Google Scholar : PubMed/NCBI
14	Bechara C and Sagan S: Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett. 587:1693–1702. 2013. View Article : Google Scholar : PubMed/NCBI
15	Kim MJ, Kim DW, Lee BR, Shin MJ, Kim YN, Eom SA, Park BJ, Cho YS, Han KH, Park J, et al: Transduced Tat-glyoxalase protein attenuates streptozotocin-induced diabetes in a mouse model. Biochem Biophys Res Commun. 430:294–300. 2013. View Article : Google Scholar
16	Song HY, Ju SM, Goh AR, Kwon DJ, Choi SY and Park J: Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes. BMB Rep. 44:462–467. 2011. View Article : Google Scholar : PubMed/NCBI
17	Kwon HY, Eum WS, Jang HW, Kang JH, Ryu J, Ryong Lee B, Jin LH, Park J and Choi SY: Transduction of Cu,Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into mammalian cells. FEBS Lett. 485:163–167. 2000. View Article : Google Scholar : PubMed/NCBI
18	Kwon HM, Choi YJ, Choi JS, Kang SW, Bae JY, Kang IJ, Jun JG, Lee SS, Lim SS and Kang YH: Blockade of cytokine-induced endothelial cell adhesion molecule expression by licorice isoliquiritigenin through NF-kappaB signal disruption. Exp Biol Med (Maywood). 232:235–245. 2007.
19	Kim MS, Kim DS, Kim HS, Kang SW and Kang YH: Inhibitory effects of luteolin on transendothelial migration of monocytes and formation of lipid-laden macrophages. Nutrition. 28:1044–1054. 2012. View Article : Google Scholar : PubMed/NCBI
20	Steed E, Balda MS and Matter K: Dynamics and functions of tight junctions. Trends Cell Biol. 20:142–149. 2010. View Article : Google Scholar : PubMed/NCBI
21	Hordijk PL: Endothelial signalling events during leukocyte transmigration. FEBS J. 273:4408–4415. 2006. View Article : Google Scholar : PubMed/NCBI
22	Carillon J, Rouanet JM, Cristol JP and Brion R: Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action. Pharm Res. 30:2718–2728. 2013. View Article : Google Scholar : PubMed/NCBI
23	Wong GH: Protective roles of cytokines against radiation: induction of mitochondrial MnSOD. Biochim Biophys Acta. 1271:205–209. 1995. View Article : Google Scholar : PubMed/NCBI
24	Holley AK, Dhar SK, Xu Y and St Clair DK: Manganese superoxide dismutase: beyond life and death. Amino Acids. 42:139–158. 2012. View Article : Google Scholar
25	Day BJ: Catalase and glutathione peroxidase mimics. Biochem Pharmacol. 77:285–296. 2009. View Article : Google Scholar :
26	Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D and Batinic-Haberle I: Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta. 1822:794–814. 2012. View Article : Google Scholar :
27	Samai M, Sharpe MA, Gard PR and Chatterjee PK: Comparison of the effects of the superoxide dismutase mimetics EUK-134 and tempol on paraquat-induced nephrotoxicity. Free Radic Biol Med. 43:528–534. 2007. View Article : Google Scholar : PubMed/NCBI
28	Sun X, Belkin N and Feinberg MW: Endothelial microRNAs and atherosclerosis. Curr Atheroscler Rep. 15:3722013. View Article : Google Scholar : PubMed/NCBI
29	Varga ZV, Giricz Z, Liaudet L, Haskó G, Ferdinandy P and Pacher P: Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy. Biochim Biophys Acta. 1852:232–242. 2015. View Article : Google Scholar
30	Han J, Shuvaev VV and Muzykantov VR: Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor. J Pharmacol Exp Ther. 338:82–91. 2011. View Article : Google Scholar : PubMed/NCBI
31	Chang M, Bany-Mohammed F, Kenney MC and Beharry KD: Effects of a superoxide dismutase mimetic on biomarkers of lung angiogenesis and alveolarization during hyperoxia with intermittent hypoxia. Am J Transl Res. 5:594–607. 2013.PubMed/NCBI
32	Kim YW, West XZ and Byzova TV: Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med Berl. 91:323–328. 2013. View Article : Google Scholar : PubMed/NCBI
33	Liu C, Wu J and Zou MH: Activation of AMP-activated protein kinase alleviates high-glucose-induced dysfunction of brain microvascular endothelial cell tight-junction dynamics. Free Radic Biol Med. 53:1213–1221. 2012. View Article : Google Scholar : PubMed/NCBI
34	Caraballo JC, Yshii C, Butti ML, Westphal W, Borcherding JA, Allamargot C and Comellas AP: Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway. Am J Physiol Lung Cell Mol Physiol. 300:L569–L578. 2011. View Article : Google Scholar : PubMed/NCBI