Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action - PubMed (original) (raw)

Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action

Hongqiao Zhang et al. Int J Biochem Cell Biol. 2011 Jul.

Abstract

Resveratrol, a polyphenolic compound rich in grapes and red wine, has been reported to protect cells against oxidative damage and cell death by increasing cellular antioxidant/detoxification capacity. Cigarette smoking is a major risk factor for respiratory diseases and oxidative damage is implicated in its pathogenesis. Here we investigated the enhancement of antioxidant capacity by resveratrol and its potential protection against cell death caused by cigarette smoke in human bronchial epithelial cells (HBE1). At concentrations that did not affect cell growth, resveratrol activated Nrf2 signaling and increased the expression of NAD(P)H:quinone reductase-1, heme oxygenase-1, and the catalytic subunit of glutamate cysteine ligase. Surprisingly, instead of protecting against cell death, resveratrol significantly enhanced cigarette smoke extract-induced apoptosis. To define the underlying mechanism, the effect of resveratrol on caspase activity was examined and it was found that resveratrol significantly enhanced cigarette smoke-stimulated caspase activity. In conclusion, results from this study suggest that although resveratrol increased antioxidant and detoxification capacity, it increased rather than protected against cigarette smoke-induced apoptosis.

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Figures

Figure 1

Figure 1

Resveratrol increased antioxidant gene expression. (A) Resveratrol increased mRNA levels of GCLC, NQO-1, and HO-1. HBE1 cells were treated with 0, 2 and 5 μM of resveratrol for 12h and mRNA level of specific gene was determined using RT-real-time PCR assay. N=3, * P<0.05 compared with vehicle control. (B) Nuclear content of Nrf2 is increased by resveratrol. HBE1 cells were treated with 5 μM resveratrol for 1 h and the nucleus was extracted and then nuclear Nrf2 level was determined with Western blotting. Lamin B1 was used as internal control.

Figure 2

Figure 2

Resveratrol enhanced CSE-induced apoptosis. (A) Resveratrol did not induce apoptosis itself. (B) Pretreatment of resveratrol increased apoptosis induced by CSE. HBE1 cells were pretreated with or without 5 μM resveratrol for 24h before being exposed to CSE for 4h. Apoptosis was then determined with annexin V-FITC method. Experiments were performed 4 times and data from one experiment was shown. The number in low-left, low-right, up-left, up-right phase shows the percentage of cells in normal condition, in the early apoptotic stage, in necrotic stage, and in late apoptotic/necrotic stage, respectively.

Figure 2

Figure 2

Resveratrol enhanced CSE-induced apoptosis. (A) Resveratrol did not induce apoptosis itself. (B) Pretreatment of resveratrol increased apoptosis induced by CSE. HBE1 cells were pretreated with or without 5 μM resveratrol for 24h before being exposed to CSE for 4h. Apoptosis was then determined with annexin V-FITC method. Experiments were performed 4 times and data from one experiment was shown. The number in low-left, low-right, up-left, up-right phase shows the percentage of cells in normal condition, in the early apoptotic stage, in necrotic stage, and in late apoptotic/necrotic stage, respectively.

Figure 3

Figure 3

Effect of resveratrol on cell growth. HBE1 cells were treated with different concentrations of resveratrol for 0 and 24 h and the cell number was counted. N=3, * P<0.05 compared with vehicle control.

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