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. 2016 Aug 31:4:e2389.
doi: 10.7717/peerj.2389. eCollection 2016.

Effect of 8-hydroxyquinoline and derivatives on human neuroblastoma SH-SY5Y cells under high glucose

Wilasinee Suwanjang  1 , Supaluk Prachayasittikul  2 , Virapong Prachayasittikul  3
Affiliations

Effect of 8-hydroxyquinoline and derivatives on human neuroblastoma SH-SY5Y cells under high glucose

Wilasinee Suwanjang et al. PeerJ. .

Abstract

8-Hydroxyquinoline and derivatives exhibit multifunctional properties, including antioxidant, antineurodegenerative, anticancer, anti-inflammatory and antidiabetic activities. In biological systems, elevation of intracellular calcium can cause calpain activation, leading to cell death. Here, the effect of 8-hydroxyquinoline and derivatives (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol and 8-hydroxy-5-nitroquinoline or nitroxoline) on calpain-dependent (calpain-calpastatin) pathways in human neuroblastoma (SH-SY5Y) cells was investigated. 8-Hydroxyquinoline and derivatives ameliorated high glucose toxicity in SH-SY5Y cells. The investigated compounds, particularly clioquinol, attenuated the increased expression of calpain, even under high-glucose conditions. 8-Hydroxyquinoline and derivatives thus adversely affected the promotion of neuronal cell death by high glucose via the calpain-calpastatin signaling pathways. These findings support the beneficial effects of 8-hydroxyquinolines for further therapeutic development.

Keywords: 8-Hydroxyquinoline; Calpain; Clioquinol; High glucose; Neuronal cells; Nitroxoline.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. 8-Hydroxyquinoline, clioquinol and nitroxoline.
(A) Chemical structures. (B) Effect of 8-hydroxyquinoline and derivatives on cell viability in SH-SY5Y cells. Cells were treated with 8-hydroxyquinoline and derivatives at 1 and 10 µM for 24 h. Cell viability was measured using the MTT assay and is presented as the percentage of control cells. The results are expressed as the mean ± S.E.M. of four independent experiments. One-way analysis of variance (ANOVA) and the Tukey-Kramer multiple comparisons test were performed for statistical analysis. **P < 0.01 and ***P < 0.001 compared with the control.
Figure 2
Figure 2. High glucose-induced alteration of cell viability, capain and capastatin proteins expression.
Cells treated with D-glucose concentrations (30, 60 and 120 mM) for 2 h and 24 h were compared to cells treated with control medium containing 5.5 mM D-glucose and mannitol as an osmotic control. (A) Cell viability was measured using the MTT assay. (B) The levels of calpain and calpastatin were determined by Western blot analysis. Protein bands were quantified by densitometry, and their differences are represented in the graph as the ratio of calpain and calpastatin to β-actin. The results are expressed as the mean + S.E.M. of four independent experiments. One-way analysis of variance (ANOVA) and Tukey-Kramer multiple comparisons test were performed for statistical analysis, *P < 0.05, **P < 0.01 and ***P < 0.001 compared with the control at 2 h and ###P < 0.001 compared with the control at 24 h.
Figure 3
Figure 3. Imaging microscopic analysis of SH-SY5Y cells demonstrating the D-glucose-induced increase in calpain expression.
Cells were treated with 120 mM D-glucose for 24 h. The control cells were incubated with the culture medium for 24 h. The green color indicates calpain immunostaining using fluorescein-5-isothiocyanate (FITC)-conjugated anti-IgG.
Figure 4
Figure 4. The effect of 8-hydroxyquinoline and derivatives on the high glucose (120 mM) in SH-SY5Y cells.
Cells were treated with high glucose for 24 h. Some cells were pre-treated with 1 µM 8-hydroxyquinoline and derivatives for 2 h prior to incubation with 120 mM high glucose for another 24 h. The control cells were incubated with the culture medium for 24 h. (A) Cell viability was measured using the MTT assay. The results are expressed as the mean ± S.E.M. of four independent experiments. (B) Calpain and (C) calpastatin expressions were determined by Western blot analysis. Protein bands were quantified by densitometry, and the changes are represented in the graph. Calpain and calpastatin expressions are presented as the ratios of calpain or calpastatin/β-actin protein bands. The results are expressed as the mean ± S.E.M. of three independent experiments. One-way analysis of variance (ANOVA) and the Tukey-Kramer multiple comparisons test were performed for statistical analysis. *P < 0.05, **P < 0.01 and ***P < 0.001 compared with the control and #P < 0.05, ##P < 0.01, ###P < 0.001 compared with high glucose-treated cells.
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Grants and funding

This project was supported by Mahidol University, Thailand, to Wilasinee Suwanjang, and by the Office of the Higher Education Commission, Mahidol University, under the National Research University Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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