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Query: EC:3.5.4.4 (
adenosine deaminase
)
5,136
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phagocytic cells respond to a variety of membrane stimulants by producing reactive oxygen intermediates (ROI), i.e. O2-, H2O2 and OH.metabolites. Plasma membrane activation is associated with superoxide generating
NADPH oxidase
, thereby causing the production of these toxic species. Stimulation of phagocytic cells also results in activation of purine catabolism, which directs the metabolic flux through xanthine oxidase to produce the superoxide anion. We previously observed that BL/LL macrophages (M phi) exhibited a premature inability to undergo tuftsin stimulated phagocytosis and microbicidal activity. The present study was undertaken to measure ROI levels in the absence and presence of 'tuftsin' pulsing as a function of in vitro culture age and also correlated these levels with
adenosine deaminase
(
ADA
) activity. The latter is known to be a contributor of O2- generation and is also involved in the maturation of the monocyte/macrophage system. The behaviour of normal and tuberculoid monocytes/macrophages were more or less the same, either in the presence or absence of tuftsin, i.e. they showed a progressive increase in ROI production until day 3, then tapered off in older cultures by day 7. In contrast, after day 1, the lepromatous macrophages were unable to undergo tuftsin mediated stimulation for the production of ROI and
ADA
activity. These findings indicate a defective M phi function in lepromatous patients towards tuftsin pulsing, thereby supporting our earlier observations. Thus BL/LL M phi behaved as if they were aged after 1 day of in vitro culture, which may account for an inability to handle Mycobacterium leprae for efficient killing.
...
PMID:Modulation of peripheral blood derived monocytes/macrophages from leprosy patients using 'tuftsin' for production of reactive oxygen intermediates. 823
The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in rat neutrophils, and the underlying mechanism of this inhibition was assessed. CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4.3 microM). In cell-free systems, CCY1a failed to alter O2(.-) generation during dihydroxyfumaric acid autoxidation, in phorbol 12-myristate 13-acetate (PMA)-activated neutrophil particulate
NADPH oxidase
preparations, or during arachidonic acid-induced
NADPH oxidase
activation. CCY1a increased cellular cyclic AMP (cAMP) levels in a time- and concentration-dependent manner, and this cAMP-elevating effect was inhibited by the adenylyl cyclase inhibitor 9-(tetrahydro-2'-furyl)adenine (SQ22536),
adenosine deaminase
(
ADA
), and the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. In neutrophils, inhibition of O2(.-) generation by CCY1a was partially reversed by the protein kinase A inhibitor (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-l][1,6]benzodiazocine-10-carboxylic acid, hexyl ester (KT5720). CCY1a did not affect fMLP-induced p38 mitogen-activated protein kinase phosphorylation, but concentration-dependently attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt (IC(50) about 31.3 and 19.4 microM, respectively). The plateau phase, but not the initial spike, of fMLP-induced [Ca2+](i) changes was inhibited by CCY1a in a concentration-dependent manner. CCY1a inhibition of Ca2+ entry, ERK, and Akt phosphorylation was not prevented by SQ22536 or
ADA
. fMLP-induced phospholipase D (PLD) activation was inhibited by CCY1a (IC(50)=13.9+/-2.0 microM).
ADA
and KT5720 did not prevent the inhibition of PLD activation by CCY1a. Collectively, these results indicate that the inhibition by CCY1a of fMLP-induced O2(.-) generation in rat neutrophils can probably be attributed to the increase in cAMP levels, and to the blockade of Ca2+ entry, suppression of Akt, and PLD activation via cAMP-independent mechanisms.
...
PMID:Investigation of the cellular mechanism of inhibition of formyl-methionyl-leucyl-phenylalanine-induced superoxide anion generation in rat neutrophils by 2-benzyloxybenzaldehyde. 1266 40
1 Chalcone is abundantly present in the plant kingdom and has various biological activities such as anti-inflammatory and antioxidant. In this study, the semisynthetic chalcone derivative, 3'-isopropoxychalcone (H2O7D), was demonstrated to inhibit the generation of superoxide and the release of elastase, as well as to accelerate resequestration of cytosolic calcium in formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils. 2 H2O7D displayed no antioxidant or superoxide-scavenging ability, and it failed to alter the subcellular
NADPH oxidase
activity. 3 H2O7D induced a substantial increase in cAMP but not cGMP levels. The elevation of cAMP formation by H2O7D was inhibited by
adenosine deaminase
(
ADA
). Furthermore, The inhibitory effects of H2O7D were reversed by protein kinase (PK)A inhibitors, as well as
ADA
and a selective A2a-receptor antagonist. 4 H2O7D inhibited phosphodiesterase (PDE) activities, but it did not alter adenylyl cyclase and soluble guanylyl cyclase activities. These results show that the cAMP-elevating effect of H2O7D results from the inhibition of PDE activity and not from the stimulation of cyclase function. Consistent with this, H2O7D potentiated the PGE(1)-caused inhibitory effects and cAMP formation. 5 In summary, these results indicate that the inhibitory effect of H2O7D is cAMP/PKA dependent, and that it occurs through inhibition of cAMP PDE, which potentiates the autocrine functions of endogenous adenosine. Inhibition of respiratory burst and degranulation in human neutrophils may give this drug the potential to protect against the progression of inflammation.
...
PMID:Inhibition of superoxide anion and elastase release in human neutrophils by 3'-isopropoxychalcone via a cAMP-dependent pathway. 1650 79
We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (
hcef2
) shows strongly increased CEF activity through the
NADPH dehydrogenase
complex (NDH), accompanied by increases in thylakoid proton motive force (
pmf
), activation of the photoprotective q
E
response, and the accumulation of H
2
O
2
. Surprisingly,
hcef2
was mapped to a non-sense mutation in the TADA1 (tRNA
adenosine deaminase
arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome
bf
complex, and the ATP synthase, suggests that inefficient translation of
hcef2
leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome
bf
hemes, and the decay kinetics of the flash-induced thylakoid electric field suggest that these defect lead to accumulation of H
2
O
2
in
hcef2
, which we have previously shown leads to activation of NDH-related CEF. We observed similar increases in CEF, as well as increases in H
2
O
2
accumulation, in other translation defective mutants. This suggests that loss of coordination in plastid protein levels lead to imbalances in photosynthetic energy balance that leads to an increase in CEF. These results taken together with a large body of previous observations, support a general model in which processes that lead to imbalances in chloroplast energetics result in the production of H
2
O
2
, which in turn activates CEF. This activation could be from either H
2
O
2
acting as a redox signal, or by a secondary effect from H
2
O
2
inducing a deficit in ATP.
...
PMID:Defects in the Expression of Chloroplast Proteins Leads to H
2
O
2
Accumulation and Activation of Cyclic Electron Flow around Photosystem I. 2813 62
