Calcium-mediated oxidative stress

A common mechanism in tight junction disruption by different types of cellular stress

Ruchika Gangwar, Avtar Meena, Pradeep Kumar Shukla, Archana S. Nagaraja, Piotr L. Dorniak, Sandeep Pallikuth, Christopher Waters, Anil Sood, Radhakrishna Rao

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo. Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca2+ by 1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N-Acetyl L-cysteine (NAC) and L-NG-Nitroarginine methyl ester (L-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and L-NAME also blocked stress-induced activation of c-Jun N-terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca2+, activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo.

Original languageEnglish (US)
Pages (from-to)731-749
Number of pages19
JournalBiochemical Journal
Volume474
Issue number5
DOIs
StatePublished - Mar 1 2017

Fingerprint

Oxidative stress
Tight Junctions
Dextran Sulfate
Oxidative Stress
Osmotic Pressure
Reactive Oxygen Species
Calcium
JNK Mitogen-Activated Protein Kinases
Chemical activation
NG-Nitroarginine Methyl Ester
Acetylcysteine
Caco-2 Cells
Monolayers
Mitochondria
Ethane
Tight Junction Proteins
Corticosterone
Sulfhydryl Compounds
Cyclosporine
Intestinal Mucosa

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Calcium-mediated oxidative stress : A common mechanism in tight junction disruption by different types of cellular stress. / Gangwar, Ruchika; Meena, Avtar; Shukla, Pradeep Kumar; Nagaraja, Archana S.; Dorniak, Piotr L.; Pallikuth, Sandeep; Waters, Christopher; Sood, Anil; Rao, Radhakrishna.

In: Biochemical Journal, Vol. 474, No. 5, 01.03.2017, p. 731-749.

Research output: Contribution to journalArticle

Gangwar, Ruchika ; Meena, Avtar ; Shukla, Pradeep Kumar ; Nagaraja, Archana S. ; Dorniak, Piotr L. ; Pallikuth, Sandeep ; Waters, Christopher ; Sood, Anil ; Rao, Radhakrishna. / Calcium-mediated oxidative stress : A common mechanism in tight junction disruption by different types of cellular stress. In: Biochemical Journal. 2017 ; Vol. 474, No. 5. pp. 731-749.
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