Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1993 Apr 11;21(7):1607–1612. doi: 10.1093/nar/21.7.1607

Protection of human endothelial cells from oxidant injury by adenovirus-mediated transfer of the human catalase cDNA.

S C Erzurum 1, P Lemarchand 1, M A Rosenfeld 1, J H Yoo 1, R G Crystal 1
PMCID: PMC309370  PMID: 8479912

Abstract

In a variety of disorders, endothelial cells are exposed to high levels of oxidants, generated within the cells and/or consequent to local inflammation. In the context of the sensitivity of endothelial cells to oxidant stress, particularly related to H2O2, we have designed a replication deficient recombinant adenovirus containing the human catalase cDNA (AdCL) to transfer the catalase cDNA to the endothelial cells, in order to augment intracellular anti-H2O2 protection. Human umbilical vein endothelial cells that were not infected or infected with control adenovirus maintained low levels of catalase mRNA. Endothelial cells infected with AdCL expressed AdCL-driven exogenous catalase mRNA, as early as 24 hr and at least for 7 days. Catalase protein levels were increased significantly over controls in cells infected with AdCL, as were catalase activity levels, with catalase activity correlated closely with levels of catalase protein. Importantly, when the endothelial cells were exposed to 500 microM H2O2, all the AdCL infected endothelial cells survived, compared to only 37% of the control cells. Thus, a recombinant adenovirus containing the human catalase cDNA is able to infect human endothelial cells in vitro and express high levels of functional intracellular catalase, protecting the cells against H2O2-mediated oxidant stress. These observations support the feasibility of the transfer of catalase cDNA to human endothelium to protect against oxidant injury.

Full text

PDF
1607

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–126. doi: 10.1016/s0076-6879(84)05016-3. [DOI] [PubMed] [Google Scholar]
  2. Amstad P., Peskin A., Shah G., Mirault M. E., Moret R., Zbinden I., Cerutti P. The balance between Cu,Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry. 1991 Sep 24;30(38):9305–9313. doi: 10.1021/bi00102a024. [DOI] [PubMed] [Google Scholar]
  3. Andreoli S. P., Mallett C. P., Bergstein J. M. Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury. J Lab Clin Med. 1986 Sep;108(3):190–198. [PubMed] [Google Scholar]
  4. Beckman J. S., Minor R. L., Jr, Freeman B. A. Augmentation of antioxidant enzymes in vascular endothelium. J Free Radic Biol Med. 1986;2(5-6):359–365. doi: 10.1016/s0748-5514(86)80036-8. [DOI] [PubMed] [Google Scholar]
  5. Beckman J. S., Minor R. L., Jr, White C. W., Repine J. E., Rosen G. M., Freeman B. A. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. J Biol Chem. 1988 May 15;263(14):6884–6892. [PubMed] [Google Scholar]
  6. Bell G. I., Najarian R. C., Mullenbach G. T., Hallewell R. A. cDNA sequence coding for human kidney catalase. Nucleic Acids Res. 1986 Jul 11;14(13):5561–5562. [PMC free article] [PubMed] [Google Scholar]
  7. Berkner K. L. Development of adenovirus vectors for the expression of heterologous genes. Biotechniques. 1988 Jul-Aug;6(7):616–629. [PubMed] [Google Scholar]
  8. Brigham K. L. Oxidant stress and adult respiratory distress syndrome. Eur Respir J Suppl. 1990 Oct;11:482s–484s. [PubMed] [Google Scholar]
  9. Brown J. M., Terada L. S., Grosso M. A., Whitmann G. J., Velasco S. E., Patt A., Harken A. H., Repine J. E. Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts. J Clin Invest. 1988 Apr;81(4):1297–1301. doi: 10.1172/JCI113448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Calabrese E. J., Canada A. T. Catalase: its role in xenobiotic detoxification. Pharmacol Ther. 1989;44(2):297–307. doi: 10.1016/0163-7258(89)90069-7. [DOI] [PubMed] [Google Scholar]
  11. Dupont G. P., Huecksteadt T. P., Marshall B. C., Ryan U. S., Michael J. R., Hoidal J. R. Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. J Clin Invest. 1992 Jan;89(1):197–202. doi: 10.1172/JCI115563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flaherty J. T., Weisfeldt M. L. Reperfusion injury. Free Radic Biol Med. 1988;5(5-6):409–419. doi: 10.1016/0891-5849(88)90115-3. [DOI] [PubMed] [Google Scholar]
  13. Freeman B. A., Crapo J. D. Biology of disease: free radicals and tissue injury. Lab Invest. 1982 Nov;47(5):412–426. [PubMed] [Google Scholar]
  14. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  15. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  16. Greenwald R. A. Superoxide dismutase and catalase as therapeutic agents for human diseases. A critical review. Free Radic Biol Med. 1990;8(2):201–209. doi: 10.1016/0891-5849(90)90092-w. [DOI] [PubMed] [Google Scholar]
  17. Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1987 Nov;1(5):358–364. [PubMed] [Google Scholar]
  18. Harlan J. M., Levine J. D., Callahan K. S., Schwartz B. R., Harker L. A. Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. J Clin Invest. 1984 Mar;73(3):706–713. doi: 10.1172/JCI111263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kinnula V. L., Whorton A. R., Chang L. Y., Crapo J. D. Regulation of hydrogen peroxide generation in cultured endothelial cells. Am J Respir Cell Mol Biol. 1992 Feb;6(2):175–182. doi: 10.1165/ajrcmb/6.2.175. [DOI] [PubMed] [Google Scholar]
  20. Lemarchand P., Jaffe H. A., Danel C., Cid M. C., Kleinman H. K., Stratford-Perricaudet L. D., Perricaudet M., Pavirani A., Lecocq J. P., Crystal R. G. Adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin cDNA to human endothelial cells. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6482–6486. doi: 10.1073/pnas.89.14.6482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lum H., Barr D. A., Shaffer J. R., Gordon R. J., Ezrin A. M., Malik A. B. Reoxygenation of endothelial cells increases permeability by oxidant-dependent mechanisms. Circ Res. 1992 May;70(5):991–998. doi: 10.1161/01.res.70.5.991. [DOI] [PubMed] [Google Scholar]
  22. Martin W. J., 2nd Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury. Am Rev Respir Dis. 1984 Aug;130(2):209–213. doi: 10.1164/arrd.1984.130.2.209. [DOI] [PubMed] [Google Scholar]
  23. McCord J. M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985 Jan 17;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  24. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  25. Patt A., Harken A. H., Burton L. K., Rodell T. C., Piermattei D., Schorr W. J., Parker N. B., Berger E. M., Horesh I. R., Terada L. S. Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains. J Clin Invest. 1988 May;81(5):1556–1562. doi: 10.1172/JCI113488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Repine J. E., Cheronis J. C., Rodell T. C., Linas S. L., Patt A. Pulmonary oxygen toxicity and ischemia-reperfusion injury. A mechanism in common involving xanthine oxidase and neutrophils. Am Rev Respir Dis. 1987 Aug;136(2):483–485. doi: 10.1164/ajrccm/136.2.483. [DOI] [PubMed] [Google Scholar]
  27. Ricevuti G., Mazzone A., Pasotti D., de Servi S., Specchia G. Role of granulocytes in endothelial injury in coronary heart disease in humans. Atherosclerosis. 1991 Nov;91(1-2):1–14. doi: 10.1016/0021-9150(91)90182-3. [DOI] [PubMed] [Google Scholar]
  28. Rosen G. M., Freeman B. A. Detection of superoxide generated by endothelial cells. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7269–7273. doi: 10.1073/pnas.81.23.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rosenfeld M. A., Siegfried W., Yoshimura K., Yoneyama K., Fukayama M., Stier L. E., Päkkö P. K., Gilardi P., Stratford-Perricaudet L. D., Perricaudet M. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science. 1991 Apr 19;252(5004):431–434. doi: 10.1126/science.2017680. [DOI] [PubMed] [Google Scholar]
  30. Rosenfeld M. A., Yoshimura K., Trapnell B. C., Yoneyama K., Rosenthal E. R., Dalemans W., Fukayama M., Bargon J., Stier L. E., Stratford-Perricaudet L. In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell. 1992 Jan 10;68(1):143–155. doi: 10.1016/0092-8674(92)90213-v. [DOI] [PubMed] [Google Scholar]
  31. Schraufstätter I., Hyslop P. A., Jackson J. H., Cochrane C. G. Oxidant-induced DNA damage of target cells. J Clin Invest. 1988 Sep;82(3):1040–1050. doi: 10.1172/JCI113660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schubert J., Wilmer J. W. Does hydrogen peroxide exist "free" in biological systems? Free Radic Biol Med. 1991;11(6):545–555. doi: 10.1016/0891-5849(91)90135-p. [DOI] [PubMed] [Google Scholar]
  33. Suttorp N., Toepfer W., Roka L. Antioxidant defense mechanisms of endothelial cells: glutathione redox cycle versus catalase. Am J Physiol. 1986 Nov;251(5 Pt 1):C671–C680. doi: 10.1152/ajpcell.1986.251.5.C671. [DOI] [PubMed] [Google Scholar]
  34. Sáez J. C., Ward P. H., Günther B., Vivaldi E. Superoxide radical involvement in the pathogenesis of burn shock. Circ Shock. 1984;12(4):229–239. [PubMed] [Google Scholar]
  35. Thimmappaya B., Weinberger C., Schneider R. J., Shenk T. Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell. 1982 Dec;31(3 Pt 2):543–551. doi: 10.1016/0092-8674(82)90310-5. [DOI] [PubMed] [Google Scholar]
  36. Turrens J. F., Crapo J. D., Freeman B. A. Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. J Clin Invest. 1984 Jan;73(1):87–95. doi: 10.1172/JCI111210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Walther F. J., Wade A. B., Warburton D., Forman H. J. Augmentation of superoxide dismutase and catalase activity in alveolar type II cells. Am J Respir Cell Mol Biol. 1991 Apr;4(4):364–368. doi: 10.1165/ajrcmb/4.4.364. [DOI] [PubMed] [Google Scholar]
  38. Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
  39. Weiss S. J., Young J., LoBuglio A. F., Slivka A., Nimeh N. F. Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest. 1981 Sep;68(3):714–721. doi: 10.1172/JCI110307. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES