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