title: Focussed microarray analysis of apoptosis in periodontitis and its potential pharmacological targeting by carvacrol.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro 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. Electronic address: fzchulia.biomed@gmail.com.
authors.forename: Fares
authors.initials: F
authors.lastname: Zeidán-Chuliá
authors.affiliation: Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland; Bacteriology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Gursoy
authors.affiliation: Centro 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.
authors.forename: Ben-Hur Neves
authors.initials: BH
authors.lastname: de Oliveira
authors.affiliation: Centro 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.
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
authors.affiliation: Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland; Bacteriology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Könönen
authors.affiliation: Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland; Bacteriology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Ulvi Kahraman
authors.initials: UK
authors.lastname: Gursoy
authors.affiliation: Centro 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.
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.affiliation: Department of Periodontology, Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors.forename: Veli-Jukka
authors.initials: VJ
authors.lastname: Uitto
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D000081007:Cymenes; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D046228:Microarray Analysis / Q000379:methods*; D039821:Monoterpenes / Q000494:pharmacology*; D018384:Oxidative Stress; D010518:Periodontitis / Q000188:drug therapy* / Q000235:genetics*; D012984:Software; D013012:Sorbitol
chemical_list: D000081007:Cymenes; D039821:Monoterpenes; D013012:Sorbitol; C073316:carvacrol; D053148:Caspase 3
keywords: Antibacterial; Antioxidant; Caspase-3; HaCaT cells; Inflammation; Monoterpenoid phenol; Oxidative stress