Reactive oxygen species control senescence-associated matrix metalloproteinase-1 through c-Jun-N-terminal kinase
Open accessAbstract
The lifetime exposure of organisms to oxidative stress influences many aging processes which involve the turnover of the extracellular matrix. In this study, we identify the redox‐responsive molecular signals that drive senescence‐associated (SA) matrix metalloproteinase‐1 (MMP‐1) expression. Precise biochemical monitoring revealed that senescent fibroblasts increase steady‐state (H 2 O 2) 3.5‐fold (13.7–48.6 pM) relative to young cells. Restricting H 2 O 2 production through low O 2 exposure or by antioxidant treatments prevented SA increases in MMP‐1 expression. The H 2 O 2‐dependent control of SA MMP‐1 is attributed to sustained JNK activation and c‐jun recruitment to the MMP‐1 promoter. SA JNK activation corresponds to increases and decreases in the levels of its activating kinase (MKK‐4) and inhibitory phosphatase (MKP‐1), respectively. Enforced MKP‐1 expression negates SA increases in JNK phosphorylation and MMP‐1 production. Overall, these studies define redox‐sensitive signaling networks regulating SA MMP‐1 expression and link the free radical theory of aging to initiation of aberrant matrix turnover. J. Cell. Physiol. 225: 52–62, 2010. © 2010 Wiley‐Liss, Inc.
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Increased expression of MMP-1 can be both age- and ROS-dependent.
“The increased expression of MMP-1 can be both age- and ROS-dependent”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [128]
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- Authors
- Dasgupta, J., Kar, S., Liu, R., Joseph, J., Kalyanaraman, B., Remington, S. J., Chen, C., & Melendez, J. A.
- Affiliations
- Albany Medical College (US)
- Medical College of Wisconsin (US)
- University of Oregon (US)
- Corresponding author
- Melendez, J. Andres
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2010-07-15
- Volume
- 225
- Issue
- 1
- Pages
- 52-62
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC2913426
- OpenAlex
- W2023237311
- Cited by
- 90
- References
- 44
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 4 · 2013: 8 · 2012: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Philip Morris International
- National Institute on Aging (AG031067, R01AG031067, AG031067-02S1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- reactive oxygen species, c-Jun N-terminal kinase, oxidative stress, MKP-1, c-Jun, hydrogen peroxide, extracellular matrix turnover, free radical theory of aging, fibroblast senescence, antioxidant treatment, low oxygen exposure, redox signaling
- MeSH terms
- Cell Line, Fibroblasts, Humans, Hydrogen Peroxide, Metalloporphyrins, Oxidation-Reduction, Oxygen, Oxidants, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, Matrix Metalloproteinase 1, MAP Kinase Signaling System, JNK Mitogen-Activated Protein Kinases, Green Fluorescent Proteins, Dual Specificity Phosphatase 1
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