Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma
Abstract
Carbonylation is an irreversible and irreparable protein modification induced by oxidative stress. Cholangiocarcinoma (CCA) is associated with chronic inflammation caused by liver fluke infection. To investigate the relationship between protein carbonylation and CCA progression, carbonylated proteins were detected by 2D OxyBlot and identified by MALDI-TOF/TOF analyses in pooled CCA tissues in comparison to adjacent nontumor tissues and normal liver tissues. We identified 14 highly carbonylated proteins in CCA tissues. Immunoprecipitation and Western blot analyses of individual samples confirmed significantly greater carbonylation of serotransferrin, heat shock protein 70-kDa protein 1 (HSP70.1), and α1-antitrypsin (A1AT) in tumor tissues compared to normal tissues. The oxidative modification of these proteins was significantly associated with poor prognoses as determined by the Kaplan-Meier method. LC-MALDI-TOF/TOF mass spectrometry identified R50, K327, and P357 as carbonylated sites in serotransferrin, HSP70.1, and A1AT, respectively. Moreover, iron accumulation was significantly higher in CCA tissues with, compared to those without, carbonylated serotransferrin. We conclude that carbonylated serotransferrin-associated iron accumulation may induce oxidative stress via the Fenton reaction, and the carbonylation of HSP70.1 with antioxidative property and A1AT with protease inhibitory capacity may cause them to become dysfunctional, leading to CCA progression.
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Iron-induced DNA damage and protein/lipid modifications may cause a more aggressive tumor cell behavior.
“In turn, this may cause a more aggressive tumor cell behavior [1,2,3].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [3]
Iron can be detrimental by contributing to free radical formation, which may provoke oxidative stress and DNA damage.
“On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage.”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [3]
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Iron as a central player and promising target in cancer progression
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- Authors
- Thanan, R., Oikawa, S., Yongvanit, P., Hiraku, Y., Ma, N., Pinlaor, S., Pairojkul, C., Wongkham, C., Sripa, B., Khuntikeo, N., Kawanishi, S., & Murata, M.
- Affiliations
- Suzuka University of Medical Science (JP)
- Mie University (JP)
- Khon Kaen University (TH)
- Corresponding author
- Kawanishi, Shosuke
- Murata, Mariko
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 52
- Issue
- 8
- Pages
- 1465-1472
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2000342553
- Cited by
- 70
- References
- 47
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 9 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 3 · 2012: 3
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Khon Kaen University (49-03-1-01-3)
- Thailand Research Fund
- Ministry of Education, Culture, Sports, Science and Technology (15406027, 19659150, 22390121)
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- cholangiocarcinoma, protein carbonylation, oxidative stress, chronic inflammation, fascioliasis, serotransferrin, HSP70, alpha-1-antitrypsin, iron accumulation, Fenton reaction, prognosis, tumor progression
- MeSH terms
- Bile Duct Neoplasms, Humans, Inflammation, Ketones, Prognosis, Proteins, Blotting, Western, Cholangiocarcinoma, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Immunoprecipitation
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