Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study is designed to test whether the postanoxic endothelial mitochondria is an important source of reactive oxygen species (ROS) using a chemical model of mitochondrial disruption to mimic the loss of mitochondrial integrity after anoxia/reoxygenation (A/R). The current objectives were to (1) determine the adhesion of human neutrophils to human umbilical vein endothelial cells exposed to antimycin A, a specific inhibitor of the mitochondrial cytochrome b-c(1) complex, and (2) define the mechanisms responsible for the early and late phases of neutrophil hyperadhesivity. Antimycin A caused a 5-fold increase in ROS generation and induced neutrophil adhesion at 30 min (phase 1) and 4 h (phase 2) that were quantitatively similar to that induced by A/R. Blockade of electron transport in antimycin A and A/R exposed cells with rotenone, amytal or thenoyltrifluoroacetate, but not myxothiazol, prevented neutrophil adhesion, confirming a role for mitochondrial ROS. Catalase inhibited phase 1 adhesion, indicating H(2)O(2) involvement. Anti-ICAM-1 or anti-P-selectin monoclonal antibodies (mAbs) attenuated phase 1 adhesion, while anti-E-selectin mAb attenuated phase 2 adhesion, consistent with roles for constitutive ICAM-1 and preformed P-selectin in early and E-selectin in late phase responses. Actinomycin D and cycloheximide or competing ds-oligonucleotides containing cognate DNA sequences of the nuclear factor kappaB or activator protein-1 attenuated phase 2 adhesion, implicating a role for de novo protein synthesis. Peak surface expression of the endothelial cell adhesion molecules correlated with peak adhesions at phases 1 and 2. These results show that disruption of mitochondrial respiratory chain elicits ROS production that mediates transcription-independent and -dependent surface expression of various adhesion molecules that leads to a two-phase neutrophil-HUVEC interaction similar to that induced by A/R.
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PMID:Role of endothelial mitochondria in oxidant production and modulation of neutrophil adherence. 1547 85