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Inhibition of glycogen synthase kinase‐3β protected human oral gingival fibroblasts from etoposide‐induced apoptosis
Author(s) -
Reddix Rhoda Ann,
Vastardis Sotirios,
Lucchesi Pamela A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1238.26
Subject(s) - gsk 3 , protein kinase b , viability assay , glycogen synthase , chemistry , apoptosis , gsk3b , etoposide , cell , mtt assay , cancer research , phosphorylation , microbiology and biotechnology , pharmacology , medicine , biochemistry , biology , chemotherapy
Background: A key feature of gingival enlargement is hyperproliferation and prolonged survival of human oral gingival fibroblasts (HOGF). Several studies have demonstrated that glycogen synthase kinase(GSK)‐3β inhibitors are cytoprotective in neurons. Their protective effects may be mediated by β‐catenin, which has also been shown to promote the survival of various cell types. Aim: To determine whether inhibition of GSK‐3β promotes the survival of HOGF cells. Methods: HOGF cells were isolated from healthy human gingival tissues obtained from two patients during periodontal surgery. The cells were grown in 24 well plates and examined for cell viability using the MTT assay. Initially, the cells were serum starved for 24 hrs, pretreated with vehicle or 10mM LiCl, a GSK‐3β inhibitor and then exposed to the pro‐apoptotic agent, etoposide (2.5 mM, ETOP). We also examined relative changes in the phosphorylation of Akt using immunoflourescence analysis in HOGF cells exposed to LiCl for 30min and 24 hrs. Results: ETOP reduced HOGF cell viability. Pretreatment with LiCl prevented the ETOP‐induced apoptosis in these cells. (p<0.01, n=6 exp). In addition, LiCl increased phosphorylated Akt levels within 30 min and it remained elevated for 24 hrs. Conclusion: The results suggest that inhibition of GSK‐3β promotes the survival of HOGF cells by activating the prosurvival protein, phosphorylated Akt. Supported by HL056046.