Zinc(II) ion promotes anti-inflammatory effects of rhSOD3 by increasing cellular association
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Recently, we demonstrated that superoxide dismutase 3 (SOD3) is a strong candidate for biomedicine. Anti-oxidant function of SOD3 was accomplished without cell penetration, and it inhibited the inflammatory responses via non-enzymatic functions. SOD3 has the heparin binding domain associating cell surface. Interestingly, we found that Zn2+ promotes transduction effects of recombinant human SOD3 (rhSOD3) by increasing uptake via the heparin binding domain (HBD). We demonstrated an uptake of rhSOD3 from media to cell lysate via HBD, resulting in an accumulation of rhSOD3 in the nucleus, which was promoted by the presence of Zn2+. This resulted in increased inhibitory effects of rhSOD3 on NF-kB and STAT3 signals in the presence of Zn2+, which shows elevated association of rhSOD3 into the cells. These results suggest that an optimized procedure can help to enhance the inflammatory efficacy of rhSOD3, as a novel biomedicine.
Abstract
Recently, we demonstrated that superoxide dismutase 3 (SOD3) is a strong candidate for biomedicine. Anti-oxidant function of SOD3 was accomplished without cell penetration, and it inhibited the inflammatory responses via non-enzymatic functions. SOD3 has the heparin binding domain associating cell surface. Interestingly, we found that Zn2+ promotes transduction effects of recombinant human SOD3 (rhSOD3) by increasing uptake via the heparin binding domain (HBD). We demonstrated an uptake of rhSOD3 from media to cell lysate via HBD, resulting in an accumulation of rhSOD3 in the nucleus, which was promoted by the presence of Zn2+. This resulted in increased inhibitory effects of rhSOD3 on NF-kB and STAT3 signals in the presence of Zn2+, which shows elevated association of rhSOD3 into the cells. These results suggest that an optimized procedure can help to enhance the inflammatory efficacy of rhSOD3, as a novel biomedicine.
참고문헌 (24)
- Serra V, "Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening", J Biol Chem, 278, pp.6824~6830 (2003)
- Teoh ML, "Overexpression of extracellular superoxide dismutase attenuates heparanase expression and inhibits breast carcinoma cell growth and invasion", Cancer Res, 69, pp.6355~6363 (2009)
- Wheeler MD, "Secretion of extracellular superoxide dismutase from muscle transduced with recombinant adenovirus inhibits the growth of B16 melanomas in mice", Mol Cancer Res, 1, pp.871~881 (2003)
- Laukkanen MO, "Adenovirus-mediated extracellular superoxide dismutase gene therapy reduces neointima formation in balloondenuded rabbit aorta", Circulation, 106, pp.1999~2003 (2002)
- Marklund SL, "Expression of extracellular superoxide dismutase by human cell lines", Biochem J, 266, pp.213~219 (1990)
- Marklund SL, "Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts", J Biol Chem, 267, pp.6696~6701 (1992)
- Stralin P, "Multiple cytokines regulate the expression of extracellular superoxide dismutase in human vascular smooth muscle cells", Atherosclerosis, 151, pp.433~441 (2000)
- Ookawara T, "Nuclear translocation of extracellular superoxide dismutase", Biochem Biophys Res Commun, 296, pp.54~61 (2002)
- Green M, "Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein", Cell, 55, pp.1179~1188 (1988)
- Frankel AD, "Cellular uptake of the tat protein from human immunodeficiency virus", Cell, 55, pp.1189~1193 (1988)
- Dixon JE, "Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides", Proc Natl Acad Sci U S A, 113, pp.E291~E299 (2016)
- WeontaeLee, "Cloning, Purification, and Characterization of Recombinant Human Extracellular Superoxide Dismutase in SF9 Insect Cells", Molecules and Cells, 39(3), pp.242~249 (2016), 한국분자세포생물학회
- Park KY, "Expression, subcellular localization, and enzyme activity of a recombinant human extra-cellular superoxide dismutase in tobacco (Nicotiana benthamiana L.)", Protein Expr Purif, 119, pp.69~74 (2016)
- 류강, "Increased Yield of High-Purity and Active Tetrameric Recombinant Human EC-SOD by Solid Phase Refolding", Journal of Microbiology and Biotechnology, 18(10), pp.1648~1654 (2008), 한국미생물·생명공학회
- Auten RL, "Transgenic extracellular superoxide dismutase protects postnatal alveolar epithelial proliferation and development during hyperoxia", Am J Physiol Lung Cell Mol Physiol, 290, pp.L32~L40 (2006)
- Gongora MC, "Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome", Am J Pathol, 173, pp.915~926 (2008)
- Juul K, "Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease", Am J Respir Crit Care Med, 173, pp.858~864 (2006)
- Oury TD, "Extracellular superoxide dismutase in vessels and airways of humans and baboons", Free Radic Biol Med, 20, pp.957~965 (1996)
- Kwon MJ, "Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice", Antioxid Redox Signal, 17, pp.1376~1392 (2012)
- 김성환, "Enhancement of potency and stability of human extracellular superoxide dismutase", BMB Reports, 48(2), pp.91~96 (2015), 생화학분자생물학회
- Kwon MJ, "Superoxide dismutase 3 suppresses hyaluronic acid fragments mediated skin inflammation by inhibition of toll-like receptor 4 signaling pathway: superoxide dismutase 3 inhibits reactive oxygen species-induced trafficking of toll-like receptor 4 to lipid rafts", Antioxid Redox Signal, 16, pp.297~313 (2012)
- Byeongwook Jeon, "Inactive extracellular superoxide dismutase disrupts secretion and function of active extracellular superoxide dismutase", BMB Reports, 44(1), pp.40~45 (2011), 생화학분자생물학회
- Kim Y, "Regulation of skin inflammation and angiogenesis by EC-SOD via HIF-1a and NF-kB pathways", Free Radic Biol Med, 51, pp.1985~1995 (2011)
- Uematsu T, "Pharmacokinetics and safety of intravenous recombinant human superoxide dismutase (NK341) in healthy subjects", Int J Clin Pharmacol Ther, 32, pp.638~641 (1994)
