Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator inhibitors (PAIs) play critical roles in regulating cellular invasion and fibrinolysis. An increase in the ratio of PAI-1/PAI-2 in placenta and maternal serum is suggested to result in excessive intervillous fibrin deposition and placental infarction in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR). In the current study we used dual (maternal and fetal) perfusion of human term placentas to examine the release of PAIs to the intervillous space. ELISA revealed a significant time-dependent increase in total PAI-1 levels in maternal perfusate (MP) between 1 and 7h of perfusion. Conversely, PAI-2 levels decreased resulting in a 3-fold increase in the PAI-1/PAI-2 ratio in MP. Levels of PAI-1, but not PAI-2, in placental tissue extracts increased during perfusion. In perfusions carried out with xanthine and xanthine oxidase (X + XO), compounds used to generate reactive oxygen species (ROS), no time-dependent increase in total PAI-1 levels was observed. In addition, X + XO treatment promoted a 3-fold reduction in active PAI-1 levels in MP, indicating that ROS decrease PAI-1 release to MP. The finding of a time-dependent change in patterns of PAI expression and response to ROS indicates the utility of dual perfusion as a model to dissect mechanism(s) promoting aberrant fibrinolysis in pregnancies complicated by PE and IUGR.
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PMID:Differential release of plasminogen activator inhibitors (PAIs) during dual perfusion of human placenta: implications in preeclampsia. 1682 Feb 3

Plasminogen activators (PAs), commonly found on the membrane of spermatozoa, convert plasminogen into plasmin and may participate in mammalian fertilization. Correlations have been reported between reactive oxygen species (ROS) and spermatozoa function, although the relationship between PA activity and ROS is unknown. We investigated the effects of ROS on PA activity. We used an in vitro model of free radical generation whereby boar spermatozoa were preincubated in xanthine and xanthine oxidase (X-XO) and PA activity was then measured. The acrosome reaction of boar spermatozoa was significantly promoted by 100 mU/mL plasmin (P<0.01), similar to levels achieved when stimulated with the positive calcium (2 mM) control. The addition of plasminogen to the fertilization medium significantly promoted both spermatozoa binding (157.5+/-14.0 spermatozoa/oocyte) and the percentage of oocytes with a male pronucleus (74.5+/-6.4%) compared with control (98.4+/-21.8 spermatozoa/oocyte and 51.4+/-5.3%, respectively; P<0.05). The acrosome reactions of spermatozoa were significantly higher when incubated with calcium (2 mM; 60.2+/-2.7%), calcium (2 mM)+EDTA (6 mM; 29.4+/-4.2%), sodium nitroprusside (0.1 microM; 38.0+/-4.2%), H(2)O(2) (100 microM; 56.0+/-3.0%), and X-XO (0.5 mM and 0.05 U/mL, respectively; 31.8+/-3.7%) compared with non-capacitation medium as control (19.0+/-2.7%; P<0.05). However, when spermatozoa were incubated with only X-XO, PA activity was significantly higher than with other treatments (P<0.05). Moreover, the addition of the antioxidant superoxide dismutase to the X-XO system significantly blocked the PA activity of spermatozoa (P<0.05). The PA activity of spermatozoa treated with X-XO was significantly reduced by the addition of MEK inhibitor (55.2+/-5.6 ng/mL) and p38 inhibitor (57.4+/-2.7 ng/mL), but not PI3K inhibitor, compared to the control (X-XO; 68.0+/-5.8 ng/mL; P<0.05). The induction of PA activity in boar spermatozoa by free radical generation suggests the PA/plasmin system plays a role in mammalian fertilization.
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PMID:Stimulation of plasminogen activator activity by free radicals in boar spermatozoa. 1901 83