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Neuroprotective Effect of Quercetin Against Hydrogen Peroxide-induced Oxidative Injury in P19 Neurons

Abstract

Oxidative stress is implicated in neuronal death in a variety of neurodegenerative diseases. In the present study, P19 neurons obtained by the differentiation procedure from mouse teratocarcinoma P19 cells were used to investigate the ability of quercetin, a plant-derived flavonoid, to prevent neuronal death induced by exposure to 150 μM or 1.5 mM hydrogen peroxide (H2O2) for 24 h. Quercetin treatment improved viability of P19 neurons exposed to both types of oxidative injury. During the modest oxidative stress, quercetin diminished generation of reactive oxygen species (ROS) and prevented H2O2-induced nuclear condensation, increase in caspase 3/7 activity and rise in poly(APD-ribose) polymerase expression. Expression of Bcl-2 family members Bax and Bcl-2 was not affected by quercetin treatment at both the transcriptional and translational levels. During the severe oxidative injury, quercetin prevented H2O2-induced rise in ROS accumulation and changes in plasma membrane integrity and nuclear morphology. The obtained results suggest that neuroprotective effects of quercetin are related to its antioxidative action and prevention of events associated with programmed cell death cascade. In the light of these findings, one might assume beneficial effects of quercetin for the prevention of oxidative stress-driven neuronal loss in human aging and age-related neurodegenerative diseases.

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Abbreviations

AIF:

Apoptosis-inducing factor

ATRA:

all-trans retinoic acid

BBB:

Blood–brain barrier

DCF-DA:

Dichlorofluorescin diacetate

DIV:

days in vitro

MTT:

3(4,5-Dimethylthiazol-2yl)2,5-dyphenyl-2H-tetrazolium bromide

PARP:

poly (ADP-ribose) polymerase

ROS:

Reactive oxygen species

NAD+ :

Nicotinamide adenine dinucleotide

RFU:

Relative fluorescence unit

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Acknowledgments

Undifferentiated P19 cells were kindly provided by Dr. J. Pachernik (Prague, Czech Republic). The skillful technical assistance to Sanjica Rak and Zlatica Tonšetić is gratefully acknowledged. The study was supported by the Croatian Ministry of Science, Education and Sport.

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Correspondence to Maja Jazvinšćak Jembrek.

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Jazvinšćak Jembrek, M., Vuković, L., Puhović, J. et al. Neuroprotective Effect of Quercetin Against Hydrogen Peroxide-induced Oxidative Injury in P19 Neurons. J Mol Neurosci 47, 286–299 (2012). https://doi.org/10.1007/s12031-012-9737-1

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  • DOI: https://doi.org/10.1007/s12031-012-9737-1

Keywords

  • Quercetin
  • Oxidative stress
  • H2O2-induced injury
  • P19 neurons
  • Neuroprotection
  • PARP expression