Role of hypohalous acids in basement membrane homeostasis
Open accessAbstract
Significance: Basement membranes (BMs) are sheet-like structures of specialized extracellular matrix that underlie nearly all tissue cell layers including epithelial, endothelial, and muscle cells. BMs not only provide structural support but are also critical for the development, maintenance, and repair of organs. Animal heme peroxidases generate highly reactive hypohalous acids extracellularly and, therefore, target BMs for oxidative modification. Given the importance of BMs in tissue structure and function, hypohalous acid-mediated oxidative modifications of BM proteins represent a key mechanism in normal development and pathogenesis of disease. Recent Advances: Peroxidasin (PXDN), a BM-associated animal heme peroxidase, generates hypobromous acid (HOBr) to form sulfilimine cross-links within the collagen IV network of BM. These cross-links stabilize BM and are critical for animal tissue development. These findings highlight a paradoxical anabolic role for HOBr, which typically damages protein structure leading to dysfunction. Critical Issues: The molecular mechanism whereby PXDN uses HOBr as a reactive intermediate to cross-link collagen IV, yet avoid collateral damage to nearby BM proteins, remains unclear. Future Directions: The exact identification and functional impact of specific hypohalous acid-mediated modifications of BM proteins need to be addressed to connect these modifications to tissue development and pathogenesis of disease. As seen with the sulfilimine cross-link of collagen IV, hypohalous acid oxidative events may be beneficial in select situations rather than uniformly deleterious. Antioxid. Redox Signal . 27, 839–854.
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Myeloperoxidase produces HOCl and other hypohalous acids such as HOBr, HOI, and HOSCN as an essential component of antimicrobial innate immunity.
“Myeloperoxidase produces HOCl and yet other hypohalous acids such as hypobromous acid HOBr, hypoiodous acid HOI, and hypothiocyanous acid HOSCN as an essential component of antimicrobial innate immunity [159].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [159]
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Functional diversity of small nucleolar RNAs
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The Role of Reactive Species on Innate Immunity
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- Authors
- Colon, S., Page-McCaw, P., & Bhave, G.
- Affiliations
- Tennessee State University (US)
- Vanderbilt University Medical Center (US)
- Vanderbilt University (US)
- Corresponding author
- Bhave, Gautam
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2017-10
- Volume
- 27
- Issue
- 12
- Pages
- 839-854
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC5647493
- OpenAlex
- W2729249620
- Cited by
- 38
- References
- 167
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 3 · 2018: 5 · 2017: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Vanderbilt University Medical Center
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK097306)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- hypohalous acids, hypobromous acid, basement membrane, peroxidasin, heme peroxidase, type IV collagen, protein oxidation, extracellular matrix, histogenesis
- MeSH terms
- Peroxidasin, Animals, Basement Membrane, Bromates, Homeostasis, Peroxidase, Extracellular Matrix Proteins, Oxidative Stress, Collagen Type IV
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