title: 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.
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.
authors: Kochi University Medical School, Kochi, Japan.
authors: Seiji
authors: S
authors: Ohno
authors: Hongfang
authors: H
authors: Yu
authors: Douglas
authors: D
authors: Dickinson
authors: Tin-Chun
authors: TC
authors: Chu
authors: Kalu
authors: K
authors: Ogbureke
authors: Scott
authors: S
authors: Derossi
authors: Tetsuya
authors: T
authors: Yamamoto
authors: Stephen
authors: S
authors: Hsu
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D000975:Antioxidants / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D004260:DNA Repair; D004195:Disease Models, Animal; D005088:Exocrine Glands / Q000378:metabolism*; D005260:Female; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D054465:Peroxiredoxin VI / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; D002392:Catechin; C045651:epigallocatechin gallate; D054465:Peroxiredoxin VI