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)

Pyocyanin is an important bacterial redox-active toxin produced by the opportunistic human pathogen Pseudomonas aeruginosa. The bacterium is a cause of serious infections of the respiratory tract, particularly for those with cystic fibrosis and for those with burn injuries. Pyocyanin induces oxidative stress and causes cells to become prematurely senescent, which compromises tissue remodeling and wound repair. A diverse range of antioxidants have been found useful in preventing oxidant-induced cellular senescence, including quercetin, a common dietary polyphenol. This study evaluated the effectiveness of three common polyphenols (quercetin, (+)-catechin, and (-)-epicatechin) as potential inhibitors of pyocyanin-induced senescence. Whereas at the lowest concentration the polyphenols maintained cellular replicative capacity, in the presence of pyocyanin they unexpectedly displayed concentration-dependent cytotoxicity with a rank order of quercetin>epicatechin>>catechin. On oxidation, polyphenols with B-ring catechol functionality form toxic alkylating quinones that are normally inactivated by cellular antioxidant defense and redox maintenance systems, including reduction by ascorbate and NAD(P)H:quinone oxidoreductase 1 (NQO1). Pyocyanin inhibited cellular NQO1 activity at low micromolar concentrations, but the presence of exogenous ascorbate eliminated pyocyanin-induced polyphenol cytotoxicity. These data indicate that pyocyanin compromises cellular redox maintenance systems, leaving cells susceptible to the adverse effects of otherwise nontoxic redox-active compounds.
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PMID:Polyphenol cytotoxicity induced by the bacterial toxin pyocyanin: role of NQO1. 1936 88

Mycobacterium abscessus (Mabs), a non-tuberculous mycobacterium, is an emerging and rapidly growing opportunistic pathogen that is frequently found in patients with cystic fibrosis and in immunosuppressed patients. Its high tolerance to antibiotics is of great concern for public health. In this study, our results showed that human THP-1-derived macrophages infected with M. abscessus presented an increase in ROS production and cell necrosis. In addition, M. abscessus infection triggered activation of the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and the induction of HO-1 and NQO1 expression levels. Interestingly, pretreatment of macrophages with sulforaphane (SFN), an activator of the antioxidant key regulator Nrf2, followed by M. abscessus infection significantly decreased mycobacterial burden. We demonstrated that this reduction in mycobacterial growth was due to an activation in cell apoptosis in SFN-pretreated and M. abscessus-infected macrophages. Pretreatment with specific MAPK inhibitors, PD98059, SP600125, and SB203580 to ERK, JNK, and p38 respectively, failed to inhibit induction of Nrf2 expression, suggesting that Nrf2 signaling pathway was upstream of MAPK signaling. Activation of cell apoptosis was caspase 3/7 independent but p38 MAPK dependent. Moreover, p38 MAPK induction was abolished in macrophages transfected with Nrf2 siRNA. In addition, p38 inhibitor abolished Nrf2-dependent apoptosis in infected macrophages. Taken together, our results indicate that modulation of the Nrf2 signaling using Nrf2 activators may help potentiate the actual drug therapies used to treat mycobacterial infection.
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PMID:Caspase-independent apoptosis in infected macrophages triggered by sulforaphane via Nrf2/p38 signaling pathways. 2755 55