[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.1007/s10059-009-0020-4

In Vivo Protein Transduction: Delivery of PEP-1-SOD1 Fusion Protein into Myocardium Efficiently Protects against Ischemic Insult

Zhang, You-en (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Wang, Jia-ning (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Tang, Jun-ming (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Guo, Ling-yun (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Yang, Jian-ye (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Huang, Yong-zhang (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Tan, Yan (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Fu, Shou-zhi (Department of Emergency, Renmin Hospital, Yunyang Medical College)
Kong, Xia (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)
Zheng, Fei (Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College)

Abstract

Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

Keywords

Cu; Zn-SOD cell-penetrating peptide; free radicals; Myocardial-reperfusion injury; PEP-1 peptide;

Citations & Related Records

Times Cited By KSCI : 2 (Citation Analysis)
Times Cited By Web Of Science : 8 (Related Records In Web of Science)

Reference
Cited By KSCI

1	Deshayes, S., Morris, M.C., Divita, G., and Heitz, F. (2005). Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol. Life Sci. 62, 1839-1849 DOI
2	Dong, X., Wang, J.N., Huang, Y.Z., Guo, L.Y., and Kong, X. (2007). Cell-penetrating peptide PEP-1-mediated transduction of enhanced green fluorescent protein into human umbilical vein endothelial cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 29, 93-97 PUBMED
3	Eum, W.S., Kim, D.W., Hwang, I.K., Yoo, K.Y., Kang, T.C., Jang, S.H., Choi, H.S., Choi, S.H., Kim, Y.H., Kim, S.Y., et al. (2004). In vivo protein transduction: biologically active intact pep-1- superoxide dismutase fusion protein efficiently protects against ischemic insult. Free Radic. Biol. Med. 37, 1656-1669 DOI ScienceOn
4	Gustafsson, A.B., Sayen, M.R., Williams, S.D., Crow, M.T., and Gottlieb, R.A. (2002). TAT protein transduction into isolated perfused hearts: TAT-apoptosis repressor with caspase recruitment domain is cardioprotective. Circulation 106, 735-739 DOI
5	Hwang, I.K., Eum, W.S., Yoo, K.Y., Cho, J.H., Kim, D.W., Choi, S.H., Kang, T.C., Kwon, O.S., Kang, J.H., Choi, S.Y., et al. (2005). Copper chaperone for Cu, Zn-SOD supplement potentiates the Cu,Zn-SOD function of neuroprotective effects against ischemic neuronal damage in the gerbil hippocampus. Free Radic. Biol. Med. 39, 392-402 DOI ScienceOn
6	Jin, L.H., Bahn, J.H., Eum, W.S., Kwon, H.Y., Jang, S.H., Han, K.H., Kang, T.C., Won, M.H., Kang, J.H., Cho, S.W., et al. (2001). Transduction of human catalase mediated by an HIV-1 TAT protein basic domain and arginine-rich peptides into mammalian cells. Free Radic. Biol. Med. 31, 1509-1519 DOI ScienceOn
7	McCord, J.M., and Fridovich, I. (1969). Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244, 6049-6055
8	Morris, M.C., Depollier, J., Mery, J., Heitz, F., and Divita, G. (2001). A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol. 19, 1173-1176 DOI ScienceOn
9	Nelson, S.K., Bose, S.K., Grunwald, G.K., Myhill, P., and McCord, J.M. (2006). The induction of human superoxide dismutase and catalase in vivo a fundamentally new approach to antioxidant therapy. Free Radic. Biol. Med. 40, 341-347 DOI ScienceOn
10	Prochiantz, A. (2000). Messenger proteins: homeoproteins, TAT and others. Curr. Opin. Cell Biol. 12, 400-406 DOI ScienceOn
11	Vives, E., Brodin, P., and Lebleu, B. (1997). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272, 16010-16017 DOI ScienceOn
12	Sayre, L.M., Smith, M.A., and Perry, G. (2001). Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr. Med. Chem. 8, 721-738 DOI ScienceOn
13	Su, J., and Kwon, H. (2003). Simultaneous determination of 4-hydroxy-2-alkenals, lipid peroxidation toxic products. Food Addit. Contam. 20, 325-330 DOI ScienceOn
14	Dalle-Donne, I., Rossi, R., Colombo, R., Giustarini, D., and Milzani, A. (2006). Biomarkers of oxidative damage in human disease. Clin. Chem. 52, 601-623 DOI PUBMED ScienceOn
15	Jenner, P. (2003). Oxidative stress in Parkinson's disease. Ann. Neurol. 53 Suppl 3, S26-36 DOI PUBMED
16	Finkel, T. (2003). Oxidant signals and oxidative stress. Curr. Opin. Cell Biol. 15, 247-254 DOI ScienceOn
17	Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L.L., Pepinsky, B., and Barsoum, J. (1994). Tat-mediated delivery of heterologous proteins into cells. Proc. Natl. Acad. Sci. USA 91, 664-668 DOI
18	Frankel, A.D., and Pabo, C.O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55, 1189-1193 DOI ScienceOn
19	Nathan, C. (2003). Specificity of a third kind: reactive oxygen and nitrogen intermediates in cell signaling. J. Clin. Invest. 111, 769-778 DOI
20	Schwarze, S.R., and Dowdy, S.F. (2000). In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNA. Trends Pharmacol. Sci. 21, 45-48 DOI ScienceOn
21	Henriques, S.T., Melo, M.N., and Castanho, M.A. (2006). Cell-penetrating peptides and antimicrobial peptides: how different are they? Biochem. J. 399, 1-7 DOI
22	Choi, H.S., An, J.J., Kim, S.Y., Lee, S.H., Kim, D.W., Yoo, K.Y., Won, M.H., Kang, T.C., Kwon, H.J., Kang, J.H., et al. (2006). PEP-1-SOD fusion protein efficiently protects against paraquatinduced dopaminergic neuron damage in a Parkinson disease mouse model. Free Radic. Biol. Med. 41, 1058-1068 DOI ScienceOn
23	Simes, J., Furberg, C.D., Braunwald, E., Davis, B.R., Ford, I., Tonkin, A., and Shepherd, J. (2000). Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The prospective pravastatin pooling project. Eur. Heart J. 23, 207-215 DOI ScienceOn
24	Choi, S.H., Kim, D.W., Kim, S.Y., An, J.J., Lee, S.H., Choi, H.S., Sohn, E.J., Hwang, S.I., Won, M.H., Kang, T.C., et al. (2005). Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death. Mol. Cells 20, 401-408 PUBMED
25	Yellon, D.M., and Baxter, G.F. (2000). Protecting the ischaemic and reperfused myocardium in acute myocardial infarction: distant dream or near reality? Heart 83, 381-387 DOI PUBMED
26	An, J.J., Lee, Y.P., Kim, S.Y., Lee, S.H., Kim, D.W., Lee, M.J., Jeong, M.S., Jang, S.H., Kang, J.H., Kwon, H.Y., et al. (2008). Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD proteins into neuronal cells. Mol. Cells 25, 55-63 PUBMED
27	Droge, W. (2002). Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47-95 DOI PUBMED
28	Haunstetter, A., and Izumo, S. (1998). Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ. Res. 82, 1111-1129 DOI PUBMED
29	Wang, J.N., Ding, P., Huang, Y.Z., Luo, L.N., Guo, L.Y., Kong, X., and Shao, F. (2007). The protective effect of PEP-1-SOD1 preconditioning on hypoxia/reoxygenation injury in cultured human umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 35, 750-756 PUBMED
30	Dhalla, N.S., Temsah, R.M., and Netticadan, T. (2000). Role of oxidative stress in cardiovascular diseases. J. Hypertens. 18, 655-673 DOI PUBMED ScienceOn
31	Kumar, D., and Jugdutt, B.I. (2003). Apoptosis and oxidants in the heart. J. Lab. Clin. Med. 142, 288-297 DOI ScienceOn

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3	(2009) Stem cell reviews and reports Non-Genetic Modulation of Notch Activity by Artificial Delivery of Notch Intracellular Domain into Neural Stem Cells / 8 (3) , 672
2	(2009) Pharmacology & therapeutics The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion / 133 (2) , 230
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9	(2009) Plant cell reports ROS-induced oxidative stress and apoptosis-like event directly affect the cell viability of cryopreserved embryogenic callus in Agapanthus praecox / 34 (9) , 1499
5	Xue-lan Liu. (2009) Biologicals : journal of the International Association of Biological Standardization The efficacy of chimeric vaccines constructed with PEP-1 and Ii-Key linking to a hybrid epitope from heterologous viruses / 43 (5) , 377
3	Xue-Gang Luo. (2016) Bioscience, biotechnology, and biochemistry Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability of human epidermal growth factor / 80 (3) , 584
6	(2009) Advanced healthcare materials Transduction Methods for Cytosolic Delivery of Proteins and Bioconjugates into Living Cells / 7 (6) , 1701040
11	(2009) Expert opinion on drug delivery Cell penetrating peptides: the potent multi-cargo intracellular carriers / 16 (11) , 1227
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