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)

Phytogenous flavonoid-containing agents (PFCA) are able to initiate electron flow bypassing the NAD-dependent region of respiratory chain, which is related with the activity of DT-diaphorase catalyzing two-electron reduction of quinones to hydroquinones and hydrogen peroxide in the presence of NADH and oxygen. This property is dramatically potentiated under the conditions of suppressed electron transport function of mitochondrial enzyme complex I (MEC I). In this process, part of the flow goes to the cytochrome region of respiratory chain and provides recovery of the MEC II and MEC III coupling function. The other part forms a flow of free oxidation which can perform as an additional mechanism normalizing the cell redox potential and aimed at decreasing intracellular acidosis under the conditions of MEC I bypassing. The energotropic effect of PFCA under the conditions of blocked MEC I is best evident at low PFCA concentrations. The ratio of coupled to free oxidation in the presence of PFCA depends on PFCA concentration. At low PFCA concentrations and oxidation of NAD-dependent substrates, both pathways become potentiated to an approximately similar extent, although the coupled oxidation pathway is generally activated earlier. At high PFCA doses, the increase in free oxidation pathway predominates and may result in toxic side effects.
 ...
PMID:[Energotropic, antihypoxic, and antioxidative effects of flavonoids]. 1739 64

Bone marrow is a major target of benzene toxicity, and NAD-(P)H:quinone oxidoreductase (NQO1), an enzyme protective against benzene toxicity, is present in human bone marrow endothelial cells, which form the hematopoietic stem cell vascular niche. In this study, we have employed a transformed human bone marrow endothelial cell (TrHBMEC) line to study the adverse effects induced by the benzene metabolite hydroquinone. Hydroquinone inhibited TrHBMEC tube formation at concentrations that were not overtly toxic, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or sulforhodamine B analysis. Hydroquinone was found to up-regulate chondromodulin-I (ChM-I), a protein that promotes chondrocyte growth and inhibits endothelial cell growth and tube formation. Recombinant human ChM-I protein inhibited tube formation in TrHBMECs, suggesting that up-regulation of ChM-I may explain the ability of hydroquinone to inhibit TrHB-MEC tube formation. To explore this possibility further, anti-ChM-I small interfering RNA (siRNA) was used to deplete ChM-I mRNA and protein. Pretreatment with anti-ChM-I siRNA markedly abrogated hydroquinone-induced inhibition of tube formation in TrHBMECs. Overexpression of the protective enzyme NQO1 in TrHBMECs inhibited the up-regulation of ChM-I and abrogated the inhibition of tube formation induced by hydroquinone. In summary, hydroquinone treatment up-regulated ChM-I and inhibited tube formation in TrHBMECs; NQO1 inhibited hydroquinone-induced up-regulation of ChM-I in TrHB-MECs and protected cells from hydroquinone-induced inhibition of tube formation. This study demonstrates that ChM-I up-regulation is one of the underlying mechanisms of inhibition of tube formation and provides a mechanism that may contribute to benzene-induced toxicity at the level of bone marrow endothelium.
 ...
PMID:Benzene metabolite hydroquinone up-regulates chondromodulin-I and inhibits tube formation in human bone marrow endothelial cells. 1952 46