Gene therapy for oxidant injury-related diseases

Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury

Claire Danel, Serpil C. Erzurum, Paule Prayssac, N. Tony Eissa, Ronald Crystal, Philippe Hervé, Bruno Baudet, Michel Mazmanian, Patricia Lemarchand

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100% O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.

Original languageEnglish
Pages (from-to)1487-1496
Number of pages10
JournalHuman Gene Therapy
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Jul 1998
Externally publishedYes

Fingerprint

Hyperoxia
Lung Injury
Reperfusion Injury
Oxidants
Adenoviridae
Genetic Therapy
Catalase
Superoxide Dismutase
Complementary DNA
Wounds and Injuries
Lung
Reperfusion
Ischemia
Immunochemistry
Alveolar Macrophages
Reactive Oxygen Species
Antioxidants
Epithelial Cells
Enzyme-Linked Immunosorbent Assay
Injections

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Gene therapy for oxidant injury-related diseases : Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury. / Danel, Claire; Erzurum, Serpil C.; Prayssac, Paule; Tony Eissa, N.; Crystal, Ronald; Hervé, Philippe; Baudet, Bruno; Mazmanian, Michel; Lemarchand, Patricia.

In: Human Gene Therapy, Vol. 9, No. 10, 01.07.1998, p. 1487-1496.

Research output: Contribution to journalArticle

Danel, Claire ; Erzurum, Serpil C. ; Prayssac, Paule ; Tony Eissa, N. ; Crystal, Ronald ; Hervé, Philippe ; Baudet, Bruno ; Mazmanian, Michel ; Lemarchand, Patricia. / Gene therapy for oxidant injury-related diseases : Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury. In: Human Gene Therapy. 1998 ; Vol. 9, No. 10. pp. 1487-1496.
@article{578d349f8472495592e4062b6340090b,
title = "Gene therapy for oxidant injury-related diseases: Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury",
abstract = "Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100{\%} O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.",
author = "Claire Danel and Erzurum, {Serpil C.} and Paule Prayssac and {Tony Eissa}, N. and Ronald Crystal and Philippe Herv{\'e} and Bruno Baudet and Michel Mazmanian and Patricia Lemarchand",
year = "1998",
month = "7",
day = "1",
doi = "10.1089/hum.1998.9.10-1487",
language = "English",
volume = "9",
pages = "1487--1496",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "10",

}

TY - JOUR

T1 - Gene therapy for oxidant injury-related diseases

T2 - Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury

AU - Danel, Claire

AU - Erzurum, Serpil C.

AU - Prayssac, Paule

AU - Tony Eissa, N.

AU - Crystal, Ronald

AU - Hervé, Philippe

AU - Baudet, Bruno

AU - Mazmanian, Michel

AU - Lemarchand, Patricia

PY - 1998/7/1

Y1 - 1998/7/1

N2 - Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100% O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.

AB - Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100% O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.

UR - http://www.scopus.com/inward/record.url?scp=0032125963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032125963&partnerID=8YFLogxK

U2 - 10.1089/hum.1998.9.10-1487

DO - 10.1089/hum.1998.9.10-1487

M3 - Article

VL - 9

SP - 1487

EP - 1496

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 10

ER -