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Title: Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression

Abstract

Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expressionmore » was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and nuclear translocation of Nrf2 resulting in the expression of antioxidant genes, leading to DNA damage suppression. These DNA lesions can be useful biomarkers to predict both the risk of BEA and the efficacy of PPIs treatment to prevent BEA in BE patients.« less

Authors:
 [1];  [2]; ; ; ;  [3];  [4]; ; ;  [5];  [1]
  1. Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)
  2. Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-0293 (Japan)
  3. Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyaki 980-8574 (Japan)
  4. Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand)
  5. Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan)
Publication Date:
OSTI Identifier:
22207835
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 421; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ANTIOXIDANTS; BIOLOGICAL MARKERS; BIOLOGICAL STRESS; CARCINOMAS; DNA; DNA DAMAGES; ESOPHAGUS; GENES; HEALTH HAZARDS; INFLAMMATION; INHIBITION; OXIDATION; OXIDIZERS; PATIENTS; SUPEROXIDE DISMUTASE; TRANSCRIPTION FACTORS; TRANSLOCATION

Citation Formats

Thanan, Raynoo, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Ma, Ning, Iijima, Katsunori, Abe, Yasuhiko, Koike, Tomoyuki, Shimosegawa, Tooru, Pinlaor, Somchai, Hiraku, Yusuke, Oikawa, Shinji, Murata, Mariko, and Kawanishi, Shosuke. Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.03.152.
Thanan, Raynoo, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Ma, Ning, Iijima, Katsunori, Abe, Yasuhiko, Koike, Tomoyuki, Shimosegawa, Tooru, Pinlaor, Somchai, Hiraku, Yusuke, Oikawa, Shinji, Murata, Mariko, & Kawanishi, Shosuke. Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression. United States. https://doi.org/10.1016/J.BBRC.2012.03.152
Thanan, Raynoo, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Ma, Ning, Iijima, Katsunori, Abe, Yasuhiko, Koike, Tomoyuki, Shimosegawa, Tooru, Pinlaor, Somchai, Hiraku, Yusuke, Oikawa, Shinji, Murata, Mariko, and Kawanishi, Shosuke. 2012. "Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression". United States. https://doi.org/10.1016/J.BBRC.2012.03.152.
@article{osti_22207835,
title = {Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression},
author = {Thanan, Raynoo and Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 and Ma, Ning and Iijima, Katsunori and Abe, Yasuhiko and Koike, Tomoyuki and Shimosegawa, Tooru and Pinlaor, Somchai and Hiraku, Yusuke and Oikawa, Shinji and Murata, Mariko and Kawanishi, Shosuke},
abstractNote = {Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expression was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and nuclear translocation of Nrf2 resulting in the expression of antioxidant genes, leading to DNA damage suppression. These DNA lesions can be useful biomarkers to predict both the risk of BEA and the efficacy of PPIs treatment to prevent BEA in BE patients.},
doi = {10.1016/J.BBRC.2012.03.152},
url = {https://www.osti.gov/biblio/22207835}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 421,
place = {United States},
year = {Fri May 04 00:00:00 EDT 2012},
month = {Fri May 04 00:00:00 EDT 2012}
}