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Focussed microarray analysis of apoptosis in periodontitis and its potential pharmacological targeting by carvacrol
Fares Zeidán-Chuliá1, Mervi Gursoy2, Ben-Hur Neves de Oliveira1
1Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Objective:
The objective of this study was to perform a landscape analysis of apoptosis-related genes/proteins and to study the differential gene expression by analysing array data from periodontitis patients and, second, to evaluate the anti-apoptotic effects of carvacrol, a monoterpenoid phenol, in vitro.
Design:
A gene/protein interaction network model 'APOP' was developed by using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) version 9.05. Differential gene expression was determined by using the limma package from R and false discovery rate (FDR). With ViaComplex software, gene expression was plotted over the network. The anti-apoptotic effect of carvacrol was tested on sorbitol-treated HaCaT cells, by using a commercial kit for caspase-3 activity.
Results:
The 'APOP' model characterised the landscape of interactions between apoptosis-related genes/proteins in silico. Forty-nine out of 70 genes from this model, such as CSF2RB, NFKBIE, ENDOG, CASP10 and CASP3, were differentially expressed (corrected p-value<0.05) in periodontitis samples when compared to those of healthy controls. In addition, carvacrol (0.43%) was able to inhibit the pro-apoptotic effects induced by sorbitol (0.3M), as seen by the reduction in caspase-3 activity on HaCaT cells.
Conclusion:
Our results suggest that caspase-3 can be a target protein to inhibit periodontitis-associated apoptosis of epithelial cells and that carvacrol has therapeutic potential as an anti-apoptotic agent.
Insights
This study analyzed apoptosis-related genes in periodontitis, finding differential expression and demonstrating carvacrol
Area of Science:
- Molecular Biology
- Genetics
- Periodontology
Background:
- Apoptosis plays a role in periodontitis pathogenesis.
- Understanding apoptosis-related gene expression is crucial for periodontitis research.
Purpose of the Study:
- To analyze the landscape of apoptosis-related genes and proteins.
- To identify differentially expressed genes in periodontitis.
- To evaluate the anti-apoptotic effects of carvacrol in vitro.
Main Methods:
- Developed an apoptosis interaction network model ('APOP').
- Analyzed gene expression data from periodontitis patients using R (limma package).
- Assessed carvacrol's effect on caspase-3 activity in sorbitol-treated HaCaT cells.
Main Results:
- The 'APOP' model mapped apoptosis-related gene interactions.
- 49 genes, including CASP3, were differentially expressed in periodontitis.
- Carvacrol inhibited sorbitol-induced apoptosis by reducing caspase-3 activity.
Conclusions:
- Caspase-3 is a potential therapeutic target for periodontitis-associated apoptosis.
- Carvacrol exhibits anti-apoptotic properties and therapeutic potential for periodontitis.
