Hybrid Malondialdehyde and Acetaldehyde Protein Adducts Form in the Lungs of Mice Exposed to Alcohol and Cigarette Smoke
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Background: Most alcohol abusers smoke cigarettes and approximately half of all cigarette smokers consume alcohol. However, no animal models of cigarette and alcohol co‐exposure exist to examine reactive aldehydes in the lungs. Cigarette smoking results in elevated lung acetaldehyde (AA) and malondialdehyde (MDA) levels. Likewise, alcohol metabolism produces AA via the action of alcohol dehydrogenase and MDA via lipid peroxidation. A high concentration of AA and MDA form stable hybrid protein adducts known as malondialdehyde–acetaldehyde (MAA) adducts. We hypothesized that chronic cigarette smoke and alcohol exposure in an in vivo mouse model would result in the in vivo formation of MAA adducts. Methods: We fed C57BL/6 mice ad libitum ethanol (20%) in drinking water and exposed them to whole‐body cigarette smoke 2 h/d, 5 d/wk for 6 weeks. Bronchoalveolar lavage fluid and lung homogenates were assayed for AA, MDA, and MAA adduct concentrations. MAA‐adducted proteins were identified by Western blot and ELISA. Results: Smoke and alcohol exposure alone elevated both AA and MDA, but only the combination of smoke + alcohol generated protein‐adducting concentrations of AA and MDA. MAA‐adducted protein (∼500 ng/ml) was significantly elevated in the smoke + alcohol‐exposed mice. Of the 5 MAA‐adducted proteins identified by Western blot, 1 protein band immunoprecipitated with antibodies to surfactant protein D. Similar to in vitro PKC stimulation by purified MAA‐adducted protein, protein kinase C (PKC) epsilon was activated only in tracheal epithelial extracts from smoke‐ and alcohol‐exposed mice. Conclusions: These data demonstrate that only the combination of cigarette smoke exposure and alcohol feeding in mice results in the generation of significant AA and MDA concentrations, the formation of MAA‐adducted protein, and the activation of airway epithelial PKC epsilon in the lung.
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Interactions between acetaldehyde or MDA and cellular proteins lead to formation of MAA adducts, which are highly stable and resistant to rapid degradation; increased MAA adducts from alcohol exposure stimulate protein dysfunction and immune-induced tissue injury through interactions with TLR-3, TLR-6, calpain, collagen alpha-1 (XII) chain, procollagen type XIV alpha-1, protocadherin beta, or补体成分.
“Interactions between acetaldehyde or MDA and cellular proteins lead to the formation of MAA adducts, which are highly stable and resistant to rapid degradation178,179.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [179]
Ethanol intake stimulates MAA adduct formation in the lung; elevated MAA adducts are found in bronchoalveolar lavage fluids of chronically alcohol-exposed animals and people with AUD; MAA adducts bind SR-A on lung macrophages to activate inflammatory processes, impede wound healing of bronchial epithelial cells, and activate PKC-mediated release of IL-8.
“Ethanol intake stimulates MAA adduct formation in the lung.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [179]
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- Authors
- McCaskill, M. L., Kharbanda, K. K., Tuma, D. J., Reynolds, J. D., DeVasure, J. M., Sisson, J. H., & Wyatt, T. A.
- Affiliations
- Nebraska Medical Center (US)
- Corresponding author
- Wyatt, Todd A.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2011-03-23
- Volume
- 35
- Issue
- 6
- Pages
- 1106-1113
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC3097262
- OpenAlex
- W1505566704
- Cited by
- 70
- References
- 52
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Kentucky
- National Institute on Alcohol Abuse and Alcoholism (R01AA017993, R37AA008769, R01AA017993-S1)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- acetaldehyde, malondialdehyde, cigarette smoke, alcohol exposure, lung, protein adducts, protein kinase C epsilon, surfactant protein D, airway epithelium, lipid peroxidation, alcohol dehydrogenase, bronchoalveolar lavage
- MeSH terms
- Acetaldehyde, Alcohol Drinking, Ethanol, Animals, Bronchoalveolar Lavage Fluid, Female, Lung, Malondialdehyde, Mice, Inbred C57BL, Smoking, DNA Adducts, Mice
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