Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that oxidative stress correlates with atrial fibrillation (AF). The purpose of the present study was to investigate the effects of reactive oxygen species (ROS) on the electrophysiological activity of human atrial myocytes. Right atrial appendages were obtained from patients with AF (AF group, n=12) and without AF (non-AF group, n=12). Single human atrial myocytes were isolated through enzymatic dissociation with type XXIV protease and type V collagenase, then divided into three subgroups: control group (n=12), H2O2 group (0.1, 0.2, 0.5, 0.75, 1, 2, 5, 10 mumol/L, n=7 at each concentration) and vitamin C (antioxidant) group (1 mumol/L, n=7). Ultrarapid delayed rectifier K(+) current (I(Kur)), L-type calcium current (I(Ca,L)) and action potential duration (APD) were recorded by whole-cell patch clamp. In AF control group, the maximum current densities of I(Kur) and I(Ca,L) were significantly lower than that in non-AF control group (both P<0.05) and APD(90) was significantly shorter as well (P<0.05). In both non-AF and AF groups, H2O2 showed two-way concentration-dependent effect on I(Kur) and I(Ca,L). The maximum current densities of I(Kur) and I(Ca,L) was significantly increased at lower H2O2 concentration, but was decreased at higher H2O2 concentration. In non-AF group, 0.2 mumol/L H2O2 caused a peak increase in the maximum current identities of I(Kur) [(8.92+/-0.51) pA/pF, P<0.05] and I(Ca,L) [(9.32+/-0.67) pA/pF, P<0.05]. H2O2 at a concentration higher than 0.75 mumol/L decreased I(Kur) and I(Ca,L). When the H2O2 concentrations were 0.2, 1, 2, 5 and 10 mumol/L, APD(90) was significantly shorter compared with that in non-AF control group (P<0.05), meanwhile it had no significant difference from that in AF control group. In AF group, the peak effective concentration of H2O2 was 0.5 mumol/L, and the turning concentration was 1 mumol/L. The H2O2 concentration-current density curve in AF group was similar to that in non-AF group, but the turning point shifted to the right, indicating that the way that H2O2 acted on ion channels in AF was the same as that in non-AF, however, the sensitivity of ion channels to H2O2 was decreased in AF. Vitamin C reversed these changes induced by H2O2, and did not affect the characteristics of ion channels. H2O2-induced electrophysiological changes in human atrial myocytes were similar to atrial electrical remodeling (AER) in AF, suggesting that ROS might induce AF. Meanwhile, H2O2 also could aggravate AER in AF, contributing to the maintenance of AF. The results suggest that antioxidants might play a significant role in the prevention and treatment of AF.
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PMID:[Two-way concentration-dependent effect of H2O2 on I(Kur) and I(Ca,L) in human atrial myocytes.]. 1908 23

Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy.
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PMID:Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model. 2589 6