Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as a significant etiological factor for disease manifestation. However, the underlying molecular mechanisms regarding areca nut chewing-induced OSF are only partially understood. Herein, we reported that arecoline markedly induced morphologic change in HaCaT epithelial cells, but had no obvious effect on Hel fibroblast cells. MTS assay revealed that arecoline significantly suppressed HaCaT cell viability. Moreover, flow cytometric analysis indicated that arecoline substantially promoted HaCaT cell, but not Hel cell apoptosis in a dose-dependent manner. Furthermore, arecoline-induced HaCaT cell apoptosis was found to be associated with increased expression and activation of cleaved-Bid, cleaved-PARA and cleaved-caspase-3. Collectively, our results suggest that HaCaT epithelial cells are more sensitive than Hel fibroblast cells to arecoline-induced cytotoxicity, which may be involved in the pathogenesis of OSF.
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PMID:Arecoline inhibits epithelial cell viability by upregulating the apoptosis pathway: implication for oral submucous fibrosis. 2464 69

Oral submucous fibrosis (OSF) is a serious, potentially malignant oral disorder. It is histopathologically characterized by chronic inflammation and atrophic epithelium accompanied by the accumulation of collagen fibers in the lamina propria. The molecular mechanisms leading to atrophic epithelium remain poorly understood. Therefore, the present study investigated the role of autophagy and apoptosis in atrophic epithelium in OSF. The expression of Caspase-3 and autophagy-related proteins (LC3 and P62) in OSF epithelial tissues was quantified by immunohistochemistry. The analysis demonstrated that, compared with normal oral mucosal tissues, autophagy and apoptosis increased with the progression of OSF. Flow cytometry and Western blotting showed that arecoline induces apoptosis in human oral keratinocytes (HOKs) in a time-dependent manner in vitro. Arecoline-induced autophagy was confirmed by transmission electron microscopy and Western blotting. When chloroquine was used as an inhibitor of autophagy, the apoptosis rate and Caspase-3 expression decreased compared with the use of arecoline alone. Thus, autophagy and apoptosis may be involved in atrophic epithelium in OSF, and arecoline-induced autophagy promotes apoptosis in HOKs.
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PMID:Role of autophagy and apoptosis in atrophic epithelium in oral submucous fibrosis. 3213 27