Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capacitation of spermatozoa is essential for fertilization and is visually characterized by hyperactivated motility. Previous reports have shown that foetal cord serum (FCS) and superoxide anion, O2.-, can trigger human sperm hyperactivation (HA) and capacitation and that superoxide dismutase (SOD) could prevent these processes. We investigated further the role of O2.- and FCS components in human sperm HA and capacitation. Percoll-washed spermatozoa were incubated, at 37 degrees C, in Ham's F-10 medium with 7.5% of FCS, dialyzed FCS (> 12 kD), ultrafiltrate from FCS (FCSu; < 3 kD), or xanthine + xanthine oxidase + catalase (X +XO + cat). Spermatozoa incubated with FCSu were also supplemented with catalase to prevent the loss of motility often observed after 2-3 h of incubation. FCS and dialyzed FCS induced significant levels of HA (10 +/- 1% and 7.7 +/- 0.7%, respectively) that were, however, lower than those observed with FCSu (19 +/- 1%) or X + XO + cat (16 +/- 2%). Similar results were obtained when the lysophosphatidylcholine-induced acrosome reaction (LPC-AR, a measure of sperm capacitation) was evaluated. The presence of SOD in the incubation medium blocked the induction of HA and capacitation by FCS, FCSu, X + XO + cat, as well as the spontaneous HA and capacitation. The enzymatic activity of SOD was needed for the prevention of these processes. Desferrioxamine, up to 100 microM, had no effect on HA and LPC-AR induced by FCSu and X + XO + cat. Addition of SOD to already hyperactivated spermatozoa reversed the HA. These data suggest that spermatozoa need a sustained O2.- generation to maintain HA and proceed to capacitation. We hypothesize that FCSu or the O2.- generated by X + XO + cat activate enzymes, possibly a reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase at the level of sperm membrane.
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PMID:Human sperm hyperactivation and capacitation as parts of an oxidative process. 838 Nov 3

Oxidized low-density lipoprotein (OxLDL) exerts proliferation and apoptosis in vascular cells, depending on its concentration and the duration of exposure. Recent studies indicate that [O(2)](-) is involved in cell cycle regulation and that OxLDL stimulates endothelial cells to produce [O(2)](-). This study examined the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a potential source for [O(2)](-) in the proliferation-inducing activity of OxLDL in cultured human umbilical vein endothelial cells (HUVEC). Human LDL was oxidized by Cu(++), and proliferation of HUVEC was detected by 3H-thymidine incorporation. OxLDL (5 microg/ml) caused an increase in proliferation of HUVEC of 250 to 300%. OxLDL-induced proliferation was blocked by addition of the antioxidants superoxide dismutase and catalase, suggesting that enhanced [O(2)](-) formation was involved. Diphenylene iodonium (DPI, 1 microM), an inhibitor of NADPH oxidase, also prevented OxLDL-induced proliferation of HUVEC, indicating that NADPH oxidase was the source for enhanced [O(2)](-) formation. The OxLDL effect was mimicked by lysophosphatidylcholine (LPC, 10 microM), a compound formed during oxidation of LDL. LPC-induced proliferation was also prevented by coincubation with DPI. Treatment of HUVEC with [O(2)](-) generated by the xanthine/xanthine oxidase reaction resulted in proliferation as did treatment with OxLDL. As expected, this stimulation could not be blocked by DPI. With the use of the cytochrome c-assay, it was demonstrated that OxLDL and LPC enhanced [O(2)](-) formation in HUVEC (by factor 3.2 and by factor 3.5, respectively). Supporting the assumption that NADPH oxidase was the enzyme responsible for [O(2)](-) formation, cells transfected with antisense oligonucleotides for NADPH oxidase showed a significantly reduced [O(2)](-) formation after stimulation with OxLDL and LPC. OxLDL and its compound LPC induce proliferation of HUVEC through activation of NADPH oxidase. The active NADPH oxidase generates [O(2)](-), which mediates the proliferative effects.
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PMID:Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells. 1100 12

1. Phospholipid metabolites lysophospholipids cause extracellular K(+) accumulation and action potential shortening with increased risk of arrhythmias during myocardial ischemia. Here we studied effects of several lysophospholipids with different lengths of hydrocarbon chains and charged headgroups on HERG K(+) currents (I(HERG)) expressed in HEK293 cells and the potential mechanisms using whole-cell patch-clamp techniques. 2. Only the lipids with 16 hydrocarbons such as 1-palmitoyl-lysophosphatidylcholine (LPC-16) and 1-palmitoyl-lysophosphatidylglycerol (LPG-16) were found to produce significant enhancement of I(HERG) and negative shifts of HERG activation, although the voltage dependence of the effects was different between LPC-16 and LPG-16 which have differently charged headgroups. The lipid with 18 hydrocarbons modestly increased I(HERG). The lipids with 6 or 24 hydrocarbons had no effect or slightly decreased I(HERG). 3. Inhibition or activation of protein kinase C did not alter the effects of LPC-16 and LPG-16. Participation of phosphatidylinositol-4,5-bisphosphate in I(HERG) enhancement by LPC-16/LPG-16 was also excluded. 4. Vitamin E augmented the effects of LPC-16/LPG-16 whereas xanthine/xanthine oxidase reduced I(HERG): indicating that LPC-16/LPG-16 produced dual effects on I(HERG): direct enhancement of I(HERG) and indirect suppression via production of superoxide anion. 5. We conclude that enhancement of HERG function by lysophospholipids is specific to the lipids with 16-hydrocarbon chain structure and the pattern of voltage dependence is determined by the polar headgroups. The increase in I(HERG) is best described by direct interactions between lipid molecules and HERG proteins, which is consistent with lack of effects via membrane destabilization or modulation by intracellular signaling pathways.
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PMID:Potential mechanisms for the enhancement of HERG K+ channel function by phospholipid metabolites. 1474 14