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Extracellular Superoxide Dismutase Induced by Dopamine in Cultured Astrocytes

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Abstract

Under some pathological conditions in brain, a large amount of superoxide anion (O2 −) is produced, causing various cellular damages. Among three isozymes of superoxide dismutase (SOD), extracellular (EC)-SOD should play a role to detoxify O2 − in extracellular space; however, a little is known about EC-SOD in brain. Although dopamine (DA) stored in the synaptic vesicle is stable, the excess leaked DA is spontaneously oxidized to yield O2 − and reactive DA quinones, causing damages of dopaminergic neurons. In the present study, we examined the effects of DA on SOD expression in cultured rat cortical astrocytes. By means of RT-PCR, all mRNA of three isozymes of SOD could be detected; however, only EC-SOD was increased by DA exposure for 24 h, dose-dependently. The expression of EC-SOD protein and the cell-surface SOD activity in astrocytes also increased with 100 μM DA exposure. The increase of EC-SOD mRNA by DA was inhibited by a DA transporter inhibitor, GBR12909, whereas it was not changed by DA receptor antagonists, SKF-83566 (D1) and haloperidol (D2). Furthermore, a monoamine oxidase inhibitor, pargyline, and antioxidants, N-acetyl-l-cysteine and glutathione, also did not affect the DA-induced expression of EC-SOD mRNA. On the other hand, an inhibitor of nuclear factor kappaB (NF-κB), ammonium pyrrolidine-1-carbodithioate, suppressed the DA-induced expression of EC-SOD mRNA. These results suggest that DA incorporated into the cells caused the induction of EC-SOD mRNA followed by the enhancements of EC-SOD protein level and the enzyme activity, and that NF-κB activation is involved in the mechanisms of the EC-SOD induction. The regulation of EC-SOD in astrocytes surrounding dopaminergic neurons may contribute to the defensive mechanism against oxidative stress in brain.

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Abbreviations

APDC:

Ammonium pyrrolidine-1-carbodithioate

DA:

Dopamine

DAT:

DA transporter

H2DCF-DA:

2′,7′-Dichlorodihydrofluorescein diacetate

DMEM:

Dulbecco’s modified Eagle medium

DTPA:

Diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GSH:

Glutathione

HKR:

HEPES-buffered Krebs–Ringer solution

HPX:

Hypoxanthine

HRP:

Horseradish peroxidase

MAO:

Monoamine oxidase

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide

NAC:

N-Acetyl-l-cysteine

NBT:

Nitrotetrazolium blue chloride

NF-κB:

Nuclear factor-kappaB

Nrf2:

NF-E2-related factor 2

O2 − :

Superoxide anion

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

WST-1:

Water soluble tetrazolium-1

XOD:

Xanthine oxidase

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Acknowledgments

This work was supported in part by a grant from the Smoking Research Foundation to Y.N. and by Grants in Aid for Scientific Research to Y.N., 24621008 and to M.M., 23580408 from the Ministry of Education, Science and Culture of Japan.

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Authors and Affiliations

  1. Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan

    Katsura Takano, Nobuyuki Tanaka, Kenji Kawabe, Mitsuaki Moriyama & Yoichi Nakamura

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  1. Katsura Takano
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  2. Nobuyuki Tanaka
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  3. Kenji Kawabe
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  4. Mitsuaki Moriyama
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Correspondence to Katsura Takano.

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Takano, K., Tanaka, N., Kawabe, K. et al. Extracellular Superoxide Dismutase Induced by Dopamine in Cultured Astrocytes. Neurochem Res 38, 32–41 (2013). https://doi.org/10.1007/s11064-012-0882-2

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  • DOI: https://doi.org/10.1007/s11064-012-0882-2

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