title: Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2.
abstract: OBJECTIVE
  Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered to be a 'master regulator' of the antioxidant response as it regulates the expression of several genes including phase II metabolic and antioxidant enzymes and thus plays an important role in preventing oxidative stress-mediated disorders, including diabetes. In this study, for the first time, we investigated the protective properties of a naturally available antioxidant, pterostilbene (PTS), against pancreatic beta-cell apoptosis and the involvement of Nrf2 in its mechanism of action.
  
  
  METHODS
  Immunoblotting and quantitative reverse transcriptase (qRT)-PCR analysis were performed to identify PTS-mediated nuclear translocation of Nrf2 protein and the following activation of target gene expression, respectively, in INS-1E cells. In addition, an annexin-V binding assay was carried out to identify the apoptotic status of PTS-treated INS-1E cells, while confirming the anti-apoptotic potential of Nrf2 by qRT-PCR analysis of the expressions of both pro- and anti-apoptotic genes.
  
  
  RESULTS
  PTS induced significant activation of Nrf2, in dose- and time-dependent manner, in streptozotocin-treated INS-1E rat pancreatic beta-cells. Furthermore, PTS increased the expression of target genes downstream of Nrf2, such as heme oxygenase 1 (HO1), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), that confer cellular protection. PTS also up-regulated the expression of anti-apoptotic gene, Bcl-2, with a concomitant reduction in pro-apoptotic Bax and caspase-3 expression.
  
  
  CONCLUSIONS
  Collectively, our findings indicate the therapeutic potential of Nrf2 activation by PTS as a promising approach to safeguard pancreatic beta-cells against oxidative damage in diabetes.
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamilnadu, India.
authors.forename: Elango
authors.initials: E
authors.lastname: Bhakkiyalakshmi
authors.forename: Devibalan
authors.initials: D
authors.lastname: Shalini
authors.forename: Thillai Veerapazham
authors.initials: TV
authors.lastname: Sekar
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Rajaguru
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
authors.forename: Kunka Mohanram
authors.initials: KM
authors.lastname: Ramkumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D013311:Streptozocin / Q000633:toxicity; D013997:Time Factors
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013267:Stilbenes; C107773:pterostilbene; D013311:Streptozocin
keywords: Nrf2; apoptosis; diabetes; pancreatic beta cells; pterostilbene; streptozotocin