Epigallocatechin-3-gallate modulates antioxidant and DNA repair-related proteins in exocrine glands of a primary Sjogren's syndrome mouse model prior to disease onset

Seiji Ohno, Hongfang Yu, Douglas Dickinson, Tin Chun Chu, Kalu Ogbureke, Scott S. DeRossi, Tetsuya Yamamoto, Stephen Hsu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.

Original languageEnglish (US)
Pages (from-to)540-546
Number of pages7
JournalAutoimmunity
Volume45
Issue number7
DOIs
StatePublished - Nov 1 2012

Fingerprint

Exocrine Glands
Sjogren's Syndrome
Peroxiredoxin VI
Proliferating Cell Nuclear Antigen
DNA Repair
Antioxidants
Proteins
Pancreas
Oxidative Stress
Biomarkers
Xerophthalmia
Xerostomia
Inbred NOD Mouse
Submandibular Gland
Polyphenols
Tea
Enzymes
Type 1 Diabetes Mellitus
Epigenomics
Catalase

Keywords

  • EGCG
  • NOD
  • PCNA
  • Salivary gland
  • Sjogren's syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Epigallocatechin-3-gallate modulates antioxidant and DNA repair-related proteins in exocrine glands of a primary Sjogren's syndrome mouse model prior to disease onset. / Ohno, Seiji; Yu, Hongfang; Dickinson, Douglas; Chu, Tin Chun; Ogbureke, Kalu; DeRossi, Scott S.; Yamamoto, Tetsuya; Hsu, Stephen.

In: Autoimmunity, Vol. 45, No. 7, 01.11.2012, p. 540-546.

Research output: Contribution to journalArticle

Ohno, Seiji ; Yu, Hongfang ; Dickinson, Douglas ; Chu, Tin Chun ; Ogbureke, Kalu ; DeRossi, Scott S. ; Yamamoto, Tetsuya ; Hsu, Stephen. / Epigallocatechin-3-gallate modulates antioxidant and DNA repair-related proteins in exocrine glands of a primary Sjogren's syndrome mouse model prior to disease onset. In: Autoimmunity. 2012 ; Vol. 45, No. 7. pp. 540-546.
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abstract = "The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.",
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AU - Yu, Hongfang

AU - Dickinson, Douglas

AU - Chu, Tin Chun

AU - Ogbureke, Kalu

AU - DeRossi, Scott S.

AU - Yamamoto, Tetsuya

AU - Hsu, Stephen

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AB - The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.

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