Cited by 620Glutathione Transferases and PolymorphismsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

Superoxide Dismutases in the Lung and Human Lung Diseases

Kinnula, Vuokko L., Crapo, James D.·2003·American Journal of Respiratory and Critical Care Medicine

Abstract

The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide. There are three SODs: cytosolic copper–zinc, mitochondrial manganese, and extracellular SODs. These enzymes have specific distributions and functions. Their importance in protecting lung tissue has been confirmed in transgenic and knockout animal studies. Relatively few studies have been conducted on these enzymes in the normal human lung or in human lung diseases. Most human studies suggest that there is induction of manganese SOD and, possibly, extracellular SOD during inflammatory, but not fibrotic, phases of parenchymal lung diseases and that both copper–zinc SOD and manganese SOD may be downregulated in asthmatic airways. Many previous antioxidant therapies have been disappointing, but newly characterized SOD mimetics are being shown to protect against oxidant-related lung disorders in animal models.

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Crossref · 10.1164/rccm.200212-1479so

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  • Manganese and copper are involved in antioxidant mechanisms through their structural role within SOD and other enzymes protecting cells from oxidative stress.

    “Manganese and copper are further trace elements involved in antioxidant mechanisms through their structural role within SOD and other crucial enzymes useful for protecting cells from OS [447,448,449].”

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Authors
Kinnula, V. L., & Crapo, J. D.
Affiliations
University of Helsinki (FI)
Venue
American Journal of Respiratory and Critical Care Medicine
Published
2003-06
Volume
167
Issue
12
Pages
1600-1619
ISSN
  • 1073-449X (ISSN-L)
  • 1535-4970
OpenAlex
W1983754228
Cited by
620
References
313
Citations by year
2026: 10 · 2025: 15 · 2024: 14 · 2023: 21 · 2022: 25 · 2021: 24 · 2020: 25 · 2019: 23 · 2018: 28 · 2017: 31 · 2016: 25 · 2015: 21 · 2014: 31 · 2013: 26 · 2012: 37
FWCI
2.57
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Respiratory and Critical Care Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (P01HL031992, K30 HL40111, U01 HL 63397, P01-HL 31992, U01HL063397)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
superoxide dismutase, copper-zinc superoxide dismutase, manganese superoxide dismutase, extracellular superoxide dismutase, oxidative stress, lung disease, asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer, antioxidant defense, superoxide dismutase mimetic, antioxidant therapy
MeSH terms
Animals, Antioxidants, Disease Models, Animal, Drug Evaluation, Preclinical, Free Radicals, Humans, Inflammation, Lung, Lung Diseases, Lung Neoplasms, Polymorphism, Genetic, Superoxide Dismutase, Genetic Therapy, Down-Regulation, Free Radical Scavengers, Reactive Oxygen Species, Lung Diseases, Interstitial, Oxidative Stress, Pulmonary Disease, Chronic Obstructive, Biomimetics

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