Interleukin-6 protects PC12 cells from 4-hydroxynonenal-induced cytotoxicity by increasing intracellular glutathione levels

Akira Nakajima, Kiyofumi Yamada, Li Bo Zou, Yijin Yan, Makoto Mizuno, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions, and it is reported that 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, is a key mediator of neuronal cell death induced by oxidative stress. Previously, we have demonstrated that interleukin-6 (IL-6) protects PC12 cells from serum deprivation and 6-hydroxydopamine-induced toxicity. Therefore, in the present study, we examined the effects of interleukins on HNE toxicity in PC12 cells. Exposure of PC12 cells to HNE resulted in a decrease in levels of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, which was due to necrotic and apoptotic cell death. Addition of IL-6 24 h before HNE treatment provided a concentration-dependent protection against HNE toxicity, whereas neither IL-1β nor IL-2 had any effect. Addition of glutathione (GSH)-ethyl ester, but not superoxide dismutase or catalase, before HNE treatment to the culture medium protected PC12 cells from HNE toxicity. We found that IL-6 increases intracellular GSH levels and the activity of γ-glutamylcysteine synthetase (γ-GCS) in PC12 cells. Buthionine sulfoximine (BSO), an inhibitor of γ-GCS, reversed the protective effect of IL-6 against HNE toxicity. These results suggest that IL-6 protects PC12 cells from HNE-induced cytotoxicity by increasing intracellular levels of GSH.

Original languageEnglish
Pages (from-to)1324-1332
Number of pages9
JournalFree Radical Biology and Medicine
Volume32
Issue number12
DOIs
Publication statusPublished - 15-06-2002
Externally publishedYes

Fingerprint

PC12 Cells
Cytotoxicity
Glutathione
Interleukin-6
Toxicity
Cell death
Cell Death
Oxidative stress
Oxidative Stress
Glutamate-Cysteine Ligase
Buthionine Sulfoximine
4-hydroxy-2-nonenal
Oxidopamine
Interleukins
Membrane Lipids
Interleukin-1
Interleukin-4
Catalase
Lipid Peroxidation
Superoxide Dismutase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Nakajima, Akira ; Yamada, Kiyofumi ; Zou, Li Bo ; Yan, Yijin ; Mizuno, Makoto ; Nabeshima, Toshitaka. / Interleukin-6 protects PC12 cells from 4-hydroxynonenal-induced cytotoxicity by increasing intracellular glutathione levels. In: Free Radical Biology and Medicine. 2002 ; Vol. 32, No. 12. pp. 1324-1332.
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Interleukin-6 protects PC12 cells from 4-hydroxynonenal-induced cytotoxicity by increasing intracellular glutathione levels. / Nakajima, Akira; Yamada, Kiyofumi; Zou, Li Bo; Yan, Yijin; Mizuno, Makoto; Nabeshima, Toshitaka.

In: Free Radical Biology and Medicine, Vol. 32, No. 12, 15.06.2002, p. 1324-1332.

Research output: Contribution to journalArticle

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AU - Nakajima, Akira

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AU - Mizuno, Makoto

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