Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase II enzymes are induced primarily through the common electrophile response element (EpRE) signaling. Studies performed in different cell types and with different inducer appear to indicate variation in the upstream signaling pathways involved in the induction of these phase II genes. Nonetheless, whether variation in signaling among phase II genes in the same cell with the same inducer is unclear. This study is designed to answer this question using human bronchial epithelial cells (HBE1 cells) as a model and screening with a variety of protein kinase inhibitors with varying degrees of specificity. Two electrophiles, 4-hydroxynonenal (HNE) and acrolein, induced the expression of phase II genes (GCLC, GCLM, NQO1, NQO2, HO-1, and GSTM-1). Nrf2 silencing significantly decreased the induction of all of these genes, confirming the involvement of Nrf2-EpRE signaling. ERK and p38MAPK inhibitors had no effect, while a JNK inhibitor abrogated the GCLC and GCLM induction by HNE, but not that by acrolein. Among the PKC inhibitors used, one eliminated gene induction by HNE and acrolein, while two others showed no effects. One PI3K inhibitor decreased the induction of GCLM, NQO1, NQO2 and HO-1, but not GCLC and GST-M1; on the other hand, the inhibitory effects of another PI3K inhibitor on gene induction seems to be gene- and inducer- specific. In conclusion, our data suggest that although phase II genes are coordinately induced through Nrf2-EpRE signaling by electrophiles, the upstream signaling pathways involved are gene- and inducer- specific. It is also suggested that commercial kinase inhibitors may produce non-specific effects on phase II gene expression via mechanisms unrelated to their purported specificity.
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PMID:Signaling pathways involved in phase II gene induction by alpha, beta-unsaturated aldehydes. 1965 97

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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PMID:Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action. 2006 Sep 27