title: Potential role of vitexin in alleviating heat stress-induced cytotoxicity: Regulatory effect of Hsp90 on ER stress-mediated autophagy.
abstract: OBJECTIVE
  Cells possess multiple methods for counteracting the deleterious consequences of stress induced by physical and chemical stimuli. Heat stress causes variations in the cellular environment, leading to cellular morbidity or mortality. Natural compounds that contain phenolic antioxidants, offer various therapeutic and biological activities. Vitexin, a natural flavonoid, has been reported to treat various pathologies due to its multifaceted effects. Herein, we investigated the therapeutic efficacy of vitexin and its underlying mechanism against heat stress in human lung epithelial cells.
  
  
  METHODS
  Effect of vitexin on the expression of molecular chaperones, antioxidant enzymes, mitogen activated protein kinases (MAPKs), endoplasmic reticulum (ER)-stress and autophagy was measured by immunoblotting. qRT-PCR and EMSA were performed for Hsp90 expression and HSF-1 binding affinity. Cell viability was assessed by MTT and LDH assays. Detection of autophagy was confirmed by acridine orange staining. Role of Hsp90 inhibition on signaling pathways was elucidated by using specific chemical inhibitor, radicicol.
  
  
  RESULTS
  Whereas hyperthermia reduced cell viability, result of MTT and LDH assays showed that vitexin pre-treatment enhanced cell viability after heat stress. EMSA analysis shows DNA binding affinity of HSF-1 during heat stress. Vitexin upregulated Hsp90 expression, subsequently activating ER-stress induced autophagy. Modulation of MAPKs expression and fluorescence image analysis showed vacuole accumulation, indicating autophagic flux in cells. Hsp90 inhibition reversed the effect of vitexin and activates the apoptosis pathway.
  
  
  CONCLUSIONS
  Our data suggest that vitexin can protect against hyperthermic cellular injury by induction of Hsp90 expression, antioxidant activity and MAPKs via ER stress-induced autophagy.
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea.
authors.forename: Monika
authors.initials: M
authors.lastname: Bhardwaj
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea.
authors.forename: Souren
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea.
authors.forename: Rekha
authors.initials: R
authors.lastname: Jakhar
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea. Electronic address: sckang@daegu.ac.kr.
authors.forename: Sun Chul
authors.initials: SC
authors.lastname: Kang
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000187:drug effects*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D047310:Apigenin; C032731:vitexin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Antioxidant activity; Autophagy; ER stress; Heat stress; Hsp90; Vitexin