title: Epigallocatechin-3-gallate prevents autoimmune-associated down- regulation of p21 in salivary gland cells through a p53-independent pathway.
abstract: The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for Sjogren's syndrome and type-1 diabetes, show an elevated level of proliferating cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant green tea catechin, normalizes the PCNA level. PCNA's activity can be regulated by the cyclin-dependent kinase inhibitor p21, which is also important for epithelial cell differentiation. In turn, expression of p21 and PCNA are partially regulated by Rb phosphorylation levels. EGCG was found to modulate p21 expression in epithelial cells, suggesting that EGCG-induced p21 could be associated with down-regulation of PCNA in vivo. The current study examined the protein levels of p21 and p53 (which can up-regulate p21) in NOD mice fed with either water or EGCG, and the effect of EGCG on p21 and p53 in cell line models with either normal or defective Rb. In NOD mice, the p21 level was low, and EGCG normalized it. In contrast to HSG cells with functional Rb, negligible expression of p21 in NS-SVAC cells that lack Rb was not altered by EGCG treatment. Inhibition of p53 by siRNA demonstrated that p21 and p53 were induced independently in HSG cells by a physiological concentration range of EGCG, suggesting p53 could be an important but not conditional factor associated with p21 expression. In conclusion, PCNA and p21 levels are altered inversely in the NOD model for SS and in HSG cells, and warrant further study as candidate new markers for salivary dysfunction associated with xerostomia. Induction of p21 by EGCG could provide clinically useful normalization of salivary glands by promoting differentiation and reducing PCNA levels.
authors: Douglas
authors: D
authors: Dickinson
authors: Hongfang
authors: H
authors: Yu
authors: Seiji
authors: S
authors: Ohno
authors: Cristina
authors: C
authors: Thomas
authors: Scott
authors: S
authors: Derossi
authors: Yat-Ho
authors: YH
authors: Ma
authors: Nicole
authors: N
authors: Yates
authors: Emily
authors: E
authors: Hahn
authors: Frederick
authors: F
authors: Bisch
authors: Tetsuya
authors: T
authors: Yamamoto
authors: AD1443 College of Dental Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA. shsu@gru.edu.
authors: Stephen
authors: S
authors: Hsu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000188:drug therapy*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014987:Xerostomia / Q000188:drug therapy*
chemical_list: D016588:Anticarcinogenic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate