Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile duct ligation (BDL)-treated rats exhibit cholestasis and increased systemic and brain oxidative stress. Activation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and disruption of the blood-brain barrier (BBB) are implicated as the pathogenetic mechanisms of brain dysfunction in BDL-treated adult rats. Young rats underwent sham ligation or BDL at day 17 for 2 or 4weeks. Treatment group rats were administered melatonin between day 17 and 45. We found a progressive increase in prefrontal cortex NADPH-dependent superoxide anion (O(2)(-)) production and increased expression of NADPH oxidase subunits in either the prefrontal cortex or the hippocampus in BDL-treated young rats. In addition, expression of intercellular adhesion molecule-1 (ICAM) and tissue plasminogen activator (t-PA) genes were increased in either the prefrontal cortex or the hippocampus. Prefrontal cortex capillary junctional complex proteins expressions including occludin, claudin-5, platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin were not altered. Melatonin lowered the prefrontal cortex NADPH-dependent O(2)(-) production and t-PA gene expression. We conclude that alterations in NADPH oxidase expression and BBB are involved in brain dysfunction in BDL-treated young rats. In addition, melatonin regulates NADPH oxidase activity and t-PA gene expression.
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PMID:Alterations in NADPH oxidase expression and blood-brain barrier in bile duct ligation-treated young rats: effects of melatonin. 2271 Mar 94

Background and Purpose- tPA (tissue-type plasminogen activator) is the only recommended intravenous thrombolytic agent for ischemic stroke. However, its application is limited because of increased risk of hemorrhagic transformation beyond the time window. T541 is a Chinese compound medicine with potential to attenuate ischemia and reperfusion injury. This study was to explore whether T541-benefited subjects underwent tPA thrombolysis extending the time window. Methods- Male C57BL/6 N mice were subjected to carotid artery thrombosis by stimulation with 10% FeCl3 followed by 10 mg/kg tPA with/without 20 mg/kg T541 intervention at 4.5 hours. Thrombolysis and cerebral blood flow were observed dynamically until 24 hours after drug treatment. Neurological deficit scores, brain edema and hemorrhage, cerebral microvascular junctions and basement membrane proteins, and energy metabolism in cortex were assessed then. An in vitro hypoxia/reoxygenation model using human cerebral microvascular endothelial cells was used to evaluate effect of T541 on tight junctions and F-actin in the presence of tPA. Results- tPA administered at 4.5 hours after carotid thrombosis resulted in a decrease in thrombus area and survival rate, whereas no benefit on cerebral blood flow. Study at 24 hours after tPA administration revealed a significant angioedema and hemorrhage in the ischemia hemisphere, a decreased expression of junction proteins claudin-5, zonula occludens-1, occludin, junctional adhesion molecule-1 and vascular endothelial cadherin, and collagen IV and laminin. Meanwhile, ADP/ATP, AMP/ATP, and ATP5D (ATP synthase subunit) expression and activities of mitochondria complex I, II, and IV declined, whereas malondialdehyde and 8-Oxo-2'-deoxyguanosine increased and F-actin arrangement disordered. All the insults after tPA treatment were attenuated by addition of T541 dose dependently. Conclusions- The results suggest T541 as a potential remedy to attenuate delayed tPA-related angioedema and hemorrhage and extend time window for tPA treatment. The potential of T541 to upregulate energy metabolism and protect blood-brain barrier is likely attributable to its effects observed.
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PMID:Angioedema and Hemorrhage After 4.5-Hour tPA (Tissue-Type Plasminogen Activator) Thrombolysis Ameliorated by T541 via Restoring Brain Microvascular Integrity. 3035 88