Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to fine particulate materials is associated with an increase in mortality rate of cardiovascular diseases. Particles deposited in the lung may affect the vascular system both directly (leaching of soluble components from particles) and indirectly (via cytokines and mediators). The present study addressed cytotoxicity and oxidative stress potency of organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) in rat heart microvessel endothelial (RHMVE) cells. The LC(50) values of OE-DEP and OE-UFP were calculated to be 17 and 34 microg/ml, respectively, suggesting that OE-DEP was more cytotoxic than OE-UFP. The viability of OE-DEP- and OE-UFP-exposed cells was ameliorated by N-acetyl-L-cysteine (NAC). The cell monolayer was exposed to 0 (control), 1, 3, and 10 microg/ml OE-DEP for 6 h and mRNA levels of antioxidant enzymes such as heme oxygenase-1 (HO-1), thioredoxin peroxidase 2 (TRPO), glutathione S-transferase P subunit (GST-P), and NADPH dehydrogenase (NADPHD) were quantitated by northern analysis. All those mRNA levels increased dose-dependently with OE-DEP and HO-1 mRNA showed the most marked response to OE-DEP. mRNA levels of those antioxidant enzymes and heat shock protein 72 (HSP72) in OE-DEP-exposed cells were higher than those of OE-UFP-exposed cells as compared at the same concentration. The transcription levels of HO-1 and HSP72 in OE-DEP- and OE-UFP-exposed cells were also reduced by NAC. Those results suggest that the organic fraction of particulate materials in the urban air has a potency to cause oxidative stress to endothelial cells and may be implicated in cardiovascular diseases through functional changes of endothelial cells.
 ...
PMID:Oxidative-stress potency of organic extracts of diesel exhaust and urban fine particles in rat heart microvessel endothelial cells. 1269 5

Intake of inorganic arsenic is known to cause vascular diseases as well as skin lesions and cancer in humans. We investigated the differences in cytotoxicity, uptake rate of arsenic, and gene expression of antioxidative enzymes between arsenite (As(3+))- and arsenate (As(5+))-exposed rat heart microvessel endothelial cells. As(3+) was more cytotoxic than As(5+), and LC(50) values were calculated to be 36 and 220 micro M, respectively. As(3+) (1-25 micro M) increased mRNA levels of antioxidant enzymes such as heme oxygenase-1 (HO-1), thioredoxin peroxidase 2, NADPH dehydrogenase, and glutathione S-transferase P subunit. HO-1 mRNA levels showed the most remarkable increase in response to As(3+). cDNA microarray analysis indicated that there was no prominent difference in arsenic-induced transcriptional changes between As(3+)- and As(5+)-exposed cells, when the cells were exposed to one-fourth the LC(50) concentration of arsenic (9 and 55 micro M for As(3+) and As(5+), respectively). N-acetyl- l-cysteine (NAC) reduced both the cytotoxicity of inorganic arsenic and the HO-1 mRNA level, and buthionine sulfoximine enhanced cytotoxicity of inorganic arsenic. As(3+) was taken up by the endothelial cells 6-7 times faster than As(5+), and the presence of NAC in the culture medium did not change the uptake rate of As(3+). These results suggest that the effects of NAC on arsenic-induced cytotoxicity and oxidative stress were due to the antioxidative role of non-protein thiols and not to chelation of arsenic in the culture medium. The difference in cellular uptake of arsenic between As(3+) and As(5+) appeared not to be due to the ionic charge on arsenic (at physiological pH, trivalent arsenic is neutral whereas pentavalent arsenic is negatively charged). These results suggest that the higher toxicity of As(3+) compared with that of As(5+) is probably due to the faster uptake of As(3+) by endothelial cells, and inorganic arsenic exerts its toxicity at least in part via intracellular oxidative stress.
 ...
PMID:Difference in uptake and toxicity of trivalent and pentavalent inorganic arsenic in rat heart microvessel endothelial cells. 1279 70