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Biochem Biophys Res Commun. 2018 Jul 12;502(2):232-237. doi: 10.1016/j.bbrc.2018.05.149. Epub 2018 May 24.

Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways.

Author information

1
Vaccine & Infectious Disease Research Centre, Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, India.
2
Vaccine & Infectious Disease Research Centre, Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, India; Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, India. Electronic address: vrati@rcb.res.in.
3
Vaccine & Infectious Disease Research Centre, Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, India. Electronic address: manjula@thsti.res.in.

Abstract

Diphenyleneiodonium (DPI) and N-acetyl-l-cysteine (NAC), two widely used anti-oxidants, were employed to evaluate the role of oxidative stress in Japanese encephalitis virus (JEV) induced autophagy, stress responses and replication. DPI and NAC exerted opposite effects on ROS levels in JEV infected mouse neuronal cells (Neuro2a), mouse embryonic fibroblasts (MEFs) and human epithelial cells (HeLa). While NAC effectively quenched ROS, DPI enhanced ROS levels, suggesting that DPI induces oxidative stress in JEV infected cells. DPI treatment of JEV infected Neuro2a cells further blocked autophagy induction and activation of all three arms of the ER stress pathway, and, inhibited virus particle release. Autophagy induction in JEV infection has been previously shown to be linked to the activation of XBP1 and ATF6 ER stress sensors. Our data suggests that DPI mediated block of autophagy is a result of inhibition of ER stress responses and is not associated with an anti-oxidative effect. Since DPI has a wide inhibitory potential for all Flavin dependent enzymes, it is likely that the signalling pathways for ER stress and autophagy during JEV infection are modulated by DPI sensitive enzymes.

KEYWORDS:

Autophagy; Diphenyleneiodonium; ER stress; Japanese encephalitis virus; N-Acetyl-l- cysteine; Reactive oxygen species

PMID:
29792860
DOI:
10.1016/j.bbrc.2018.05.149
[Indexed for MEDLINE]

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