PMID- 26475763
OWN - NLM
STAT- MEDLINE
DCOM- 20160222
LR  - 20171116
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 142
DP  - 2015 Dec 1
TI  - Potential role of vitexin in alleviating heat stress-induced cytotoxicity: 
      Regulatory effect of Hsp90 on ER stress-mediated autophagy.
PG  - 36-48
LID - S0024-3205(15)30038-2 [pii]
LID - 10.1016/j.lfs.2015.10.012 [doi]
AB  - AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Bhardwaj, Monika
AU  - Bhardwaj M
AD  - Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, 
      Republic of Korea.
FAU - Paul, Souren
AU  - Paul S
AD  - Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, 
      Republic of Korea.
FAU - Jakhar, Rekha
AU  - Jakhar R
AD  - Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, 
      Republic of Korea.
FAU - Kang, Sun Chul
AU  - Kang SC
AD  - Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, 
      Republic of Korea. Electronic address: sckang@daegu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151021
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Cytotoxins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Heat Shock Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 7V515PI7F6 (Apigenin)
RN  - 9VP70K75OK (vitexin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Apigenin/*pharmacology
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor
MH  - Cytotoxins/*pharmacology
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - Heat Shock Transcription Factors
MH  - Heat-Shock Response/*drug effects
MH  - Humans
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - Antioxidant activity
OT  - Autophagy
OT  - ER stress
OT  - Heat stress
OT  - Hsp90
OT  - Vitexin
EDAT- 2015/10/18 06:00
MHDA- 2016/02/24 06:00
CRDT- 2015/10/18 06:00
PHST- 2015/07/06 00:00 [received]
PHST- 2015/09/25 00:00 [revised]
PHST- 2015/10/10 00:00 [accepted]
PHST- 2015/10/18 06:00 [entrez]
PHST- 2015/10/18 06:00 [pubmed]
PHST- 2016/02/24 06:00 [medline]
AID - S0024-3205(15)30038-2 [pii]
AID - 10.1016/j.lfs.2015.10.012 [doi]
PST - ppublish
SO  - Life Sci. 2015 Dec 1;142:36-48. doi: 10.1016/j.lfs.2015.10.012. Epub 2015 Oct 21.