PMID- 28656249
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20211110
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 3
DP  - 2017 Sep
TI  - Oxidative stress regulates mitogen‑activated protein kinases and c‑Jun activation 
      involved in heat stress and lipopolysaccharide‑induced intestinal epithelial cell 
      apoptosis.
PG  - 2579-2587
LID - 10.3892/mmr.2017.6859 [doi]
AB  - Heat stress and gut‑derived endotoxinemia are common causes of multiple organ 
      dysfunction syndrome in heat stroke patients. Evidence has demonstrated that cell 
      apoptosis in the small intestine serves an important role in the pathogenesis of 
      heatstroke, which leads to increased intestinal permeability to endotoxin or 
      lipopolysaccharides (LPS) from the gut entering the circulation. However, little 
      is known about the potential underlying mechanisms mediating heat stress combined 
      with LPS‑induced intestinal epithelial cell apoptosis. In the present study, LPS 
      combined with heat stress induced production of reactive oxygen species (ROS), 
      mitochondrial membrane potential disruption and cell apoptosis, which eventually 
      led to increased intestinal permeability and reduced epithelial resistance in the 
      IEC‑6 cell line. Inductions in ROS, mitochondrial membrane potential disruption 
      and cell apoptosis were detected by using an ROS assay kit, 
      5,5',6,6'‑tetrachloro‑1,1',3,3'tetraethylbenzimidazo carbocyanine iodide dye kit 
      and annexin V‑fluorescein isothiocyanate apoptosis kit, respectively. The effect 
      of ROS on mitogen activated protein kinases (MAPKs) and c‑Jun activation was 
      investigated using the antioxidant drug, butylated hydroxyanisole (BHA) by 
      western blotting. The results of the present study demonstrated that ROS is 
      essential to activate p38, extracellular signal‑regulated kinase (ERK) and c‑Jun, 
      but not c‑Jun N‑terminal kinase (JNK), in LPS combined with heat stress treated 
      cells. Furthermore, ROS, and activation of p38, JNK and c‑Jun, were revealed to 
      serve pro‑apoptosis roles which aggravated damage to epithelial barrier 
      integrity, as assessed by flow cytometry using Annexin V‑fluorescein 
      isothiocyanate staining and pretreatment of cells with specific inhibitors of 
      ROS, JNK, p38 and c‑Jun (BHA, SP600125, SB203580 and c‑Jun peptide, 
      respectively). Transepithelial electrical resistance and horseradish peroxidase 
      permeability were detected in cells treated with LPS combined with heat stress, 
      which revealed that ERK serves an anti‑apoptosis role, as determined by 
      pretreatment of cells with PD98059, a specific inhibitor of ERK. In conclusion, 
      these findings suggested a novel role of the ROS signaling pathway which involved 
      activation of MAPKs and c‑Jun, following LPS combined with heat stress‑induced 
      IEC‑6 cell apoptosis and impairment of the epithelial barrier. These results may 
      facilitate understanding of pathological conditions involving ROS, such as heat 
      stroke.
FAU - Liu, Yanan
AU  - Liu Y
AD  - Department of Intensive Care Unit, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Wang, Zhenglian
AU  - Wang Z
AD  - Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 
      510120, P.R. China.
FAU - Xie, Weidang
AU  - Xie W
AD  - The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 
      Guangdong 510000, P.R. China.
FAU - Gu, Zhengtao
AU  - Gu Z
AD  - Department of Intensive Care Unit, The Third Affiliated Hospital of Southern 
      Medical University, Guangzhou, Guangdong 510630; P.R. China.
FAU - Xu, Qiulin
AU  - Xu Q
AD  - Department of ICU, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair 
      of PLA, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 
      510010, P.R. China.
FAU - Su, Lei
AU  - Su L
AD  - Department of ICU, Key Laboratory of Tropical Zone Trauma Care and Tissue Repair 
      of PLA, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 
      510010, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170627
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - *Apoptosis
MH  - Caco-2 Cells
MH  - Cell Line
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Heat-Shock Response
MH  - Humans
MH  - Intestinal Mucosa/*cytology/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Lipopolysaccharides/*metabolism
MH  - Membrane Potential, Mitochondrial
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - *Oxidative Stress
MH  - Permeability
MH  - Reactive Oxygen Species/metabolism
PMC - PMC5548022
EDAT- 2017/06/29 06:00
MHDA- 2018/05/01 06:00
PMCR- 2017/06/27
CRDT- 2017/06/29 06:00
PHST- 2016/04/17 00:00 [received]
PHST- 2017/03/23 00:00 [accepted]
PHST- 2017/06/29 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/06/29 06:00 [entrez]
PHST- 2017/06/27 00:00 [pmc-release]
AID - mmr-16-03-2579 [pii]
AID - 10.3892/mmr.2017.6859 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Sep;16(3):2579-2587. doi: 10.3892/mmr.2017.6859. Epub 2017 Jun 
      27.