Molecular and Cellular Biochemistry

, Volume 354, Issue 1–2, pp 97–112 | Cite as

Stabilization of Nrf2 by tBHQ prevents LPS-induced apoptosis in differentiated PC12 cells

Article

Abstract

The inflammatory reaction plays an important role in the pathogenesis of the neurodegenerative disorders. tert-butylhydroquinone (tBHQ) exhibits a wide range of pharmacological activities including anti-oxidative and anti-inflammatory action. In this study, we tried to elucidate possible effects of tBHQ on lipopolysaccharide (LPS)-induced inflammatory reaction and its underlying mechanism in neuron-like PC12 cells. tBHQ inhibited LPS-induced generation of reactive oxygen species (ROS) and elevation of intracellular calcium level. It also inhibited LPS-induced cyclooxygenase 2 (COX-2), TNF-α, nuclear factor KappaB (NF-kB), and caspase-3 expression in a dose-dependent manner while stabilizing nuclear factor-erythroid 2 p45-related factor 2. Moreover, the phosphorylations of p38, ERK1/2, and JNK were suppressed by tBHQ. These results suggest that the anti-inflammatory properties of tBHQ might result from inhibition of COX-2 and TNF-α expression, inhibition of NF-kB nuclear translocation along with suppression of MAP kinases (p38, ERK1/2, and JNK) phosphorylation in PC12 cells, so may be a useful agent for prevention of inflammatory diseases.

Keywords

Lipopolysaccharide Mitogen-activated protein kinase NF-κB PC12 cells tBHQ 

Abbreviations

Amyloid β

AREs

Antioxidant responsive elements

CAT

Catalase

CNS

Central nervous system

ECL

Electrochemiluminescence

GSH

Glutathione

H2O2

Hydrogen peroxide

Keap1

Kelch-like ECH-associated protein 1

MDA

Malondialdehyde

MTT

3-[4,5-Dimethylthiazol-2-yl]-2, 5-dephenyl tetrazolium bromide

NF-κB

Nuclear factor-κB

NGF

Nerve growth factor

Nrf2

Nuclear factor-erythroid 2 p45-related factor 2

ROS

Reactive oxygen species

SOD

Superoxide dismutase

tBHQ

tert-Butylhydroquinone

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran

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