Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparison has been made between the effects of 4-hydroxy-2,3-trans-nonenal (HNE) and 4-hydroxy-2,3-trans-octenal (HOE), two lipid peroxidation products, on the basal and GTPgammaS-stimulated activities of phosphoinositide-specific phospholipase C (PL-C) of rat polymorphonuclear leukocytes. PL-C activity was determined in vitro by measuring the hydrolysis of [3H] phosphatidylinositol-4,5-bis- phosphate (PtdIns-P2) added as exogenous substrate to neutrophil plasma membranes. PL-C was activated by concentrations of HNE ranging from 10(-8) to 10(-6) M both in the presence and in the absence of 2 x 10(-5) M GTPgammaS; HOE stimulated the enzymatic activity between 10(-11) and 10(-8) M; maximal stimulation was given by 10(-11) M HOE plus GTPgammaS. The aldehyde concentrations able to accelerate PtdIns-P2 breakdown displayed a good correspondence with those which have been reported to stimulate the oriented migration of rat neutrophils. Pretreatment of neutrophils with pertussis toxin prevented the stimulation of PL-C by 10(-11) M HOE and by HOE plus GTPgammaS. Our results suggest that the chemotactic action of HNE and HOE might depend on the activation of PL-C; furthermore a regulatory G protein appears to be involved in the acceleration of PtdIns-P2 turnover by HOE.
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PMID:Activation of phosphoinositide-specific phospholipase C of rat neutrophils by the chemotactic aldehydes 4-hydroxy-2,3-trans-nonenal and 4-hydroxy-2,3-trans-octenal. 783 17

2-Iodohexadecanal (IHDA), which can be formed upon addition of iodine to the vinyl ether group of plasmalogens, has been identified as a major thyroid iodolipid (Pereira et al. (1990) J. Biol. Chem. 265, 17018-17025). In this study, we have investigated the possibility that it would be a mediator of the inhibitory effect of iodide on thyroid adenylyl cyclase. In human thyroid membranes, IHDA inhibited the adenylyl cyclase activity stimulated by thyrotropin (TSH), GTP-gamma-S or forskolin (FSK), whereas it did not decrease the specific binding of TSH to its receptors. The inhibitory effect on the cyclase reached a maximum after a 1-h-pre-incubation of the membranes with IHDA at 30 degrees C and was poorly reversible. It was also observed following a 4-h incubation with IHDA at 4 degrees C, a condition in which adenylyl cyclase is protected against heat inactivation. IHDA decreased the Vmax of adenylyl cyclase, but had no effect on the Km for ATPMg2-.IHDA also inhibited the FSK-stimulated adenylyl cyclase activity in liver and kidney cortex membranes, but had no effect on the Mg(2+)-ATPase activity of thyroid membranes. The inhibitory effect of IHDA has also been demonstrated in intact cells. As in membranes, IHDA decreased the rise in cAMP induced by TSH in cultured dog thyroid cells and this inhibition was maintained following pretreatment of the cells with pertussis toxin. In order to evaluate the specificity of the IHDA action, various analogs have been synthesized. This study has permitted the identification of two major structural features required for the inhibition of human thyroid adenylyl cyclase; the terminal aldehyde function and an iodine atom at C2, other halogens being ineffective. In conclusion, we have shown that IHDA exerts a direct inhibitory effect at or near adenylyl cyclase; all the properties of this effect characterized so far are identical to those of the adenylyl cyclase inhibition obtained following the exposure of thyroid tissue to iodide.
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PMID:Inhibition of human thyroid adenylyl cyclase by 2-iodoaldehydes. 789 13

4-Hydroxynonenal (HNE), a major lipid peroxidation product, displays several biological actions. Among them, the differentiation of human HL-60 cells and the stimulation of neutrophil oriented migration occur at concentrations which can be actually found in normal tissues and in body fluids. In spite of its chemotactic activity, HNE fails to increase neutrophil oxidative metabolism. The action of the aldehyde on cell migration appears to be mediated by a phosphoinositide specific phospholipase C. The acceleration of phosphatidylinositol turnover induced by 10 pM 4-hydroxyoctenal, another lipid peroxidation product, is prevented by the pretreatment of neutrophils with pertussis toxin. The mechanism of action of these 4-hydroxyalkenals appears to follow pathways common to other chemoattractants, but some differences can be found too. In particular HNE seems unable to stimulate phospholipase D activity. The action of 4-hydroxyalkenals and other lipid peroxidation products on transmembrane signalling systems and on phospholipid metabolism might regulate several cell functions, such as motility, proliferation and differentiation.
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PMID:Action of lipid peroxidation products on phosphoinositide specific phospholipase C. 826 43

Physico-chemical methods are being developed for use in the control and standardization of acellular pertussis vaccines and their individual components. We have compared native and detoxified preparations of the B. pertussis antigens, pertussis toxin (PT), filamentous haemagglutinin (FHA), and the 69-kDa outer membrane protein (P69) using circular dichroism (CD), fluorescence spectroscopy, SDS-PAGE and FPLC gel filtration chromatography. Upon aldehyde detoxification, PT underwent a large change in its intrinsic fluorescence maximum (8-10 nm red-shift) and a large increase in its apparent size, detected by chromatography. Polyacrylamide gels showed individual subunits of the same apparent molecular weight (M(r)) as well as some polypeptides of higher M(r). FHA also changed conformation (5-nm red-shift in intrinsic fluorescence) upon aldehyde detoxification, with a resultant increase in the M(r)of its major constituent. The P69 protein appeared quite robust to formaldehyde treatment as measured by the same methods. Its near-UV CD spectrum contains a prominent tryptophan band; so this method may be more suitable for observing differences in conformation. We also examined an aluminium-desorbed DTaP preparation by these methods. When used in conjunction with immunochemical and toxicological assays, these methods are informative and useful in the characterization of candidate standards and should be valuable methods for ensuring the consistency of manufactured vaccines.
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PMID:Physico-chemical analysis of Bordetella pertussis antigens. 1060 Feb 5

The action of 4-hydroxynonenal (HNE), a chemotactic aldehyde produced by lipid peroxidation, was analysed on exocytosis in parallel with its effects on phosphoinositide-specific phospholipase C (PLC) both in undifferentiated HL-60 cells and in cells induced to differentiate toward the granulocytic cell line by 1.25% DMSO. Exocytosis was evaluated by the secretion of beta-glucuronidase from cells incubated at 37 degrees C for 10 min in the presence of various aldehyde concentrations. HNE action was more pronounced in DMSO-differentiated cells, where concentrations between 10(-8) and 10(-6) m were able both to trigger exocytosis and to strongly activate PLC; in both processes maximal stimulation was given by 10(-7) m. HNE-induced exocytosis was completely prevented by pertussis toxin and by the PLC inhibitor U73122. The comparison between HNE and formyl-methionyl-leucyl-phenylalanine (fMLP), used as a positive control, showed that the tripeptide produced an higher stimulation of exocytosis than the aldehyde; by contrast HNE induced a stronger increase of PLC activity. Wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI3K), strongly inhibited the exocytosis induced by fMLP, while it failed to induce a statistically significant inhibition of HNE action. We conclude that both compounds trigger exocytosis through a Ptx-sensitive G protein; the present data support the hypothesis that the lower ability of the aldehyde to trigger exocytosis as compared to fMLP might depend upon a low ability to activate PI3K, while PLC activation appears to play a key role in HNE-induced exocytosis.
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PMID:Experimental researches on the role of phosphoinositide-specific phospholipase C in 4-hydroxynonenal induced exocytosis. 1273 5

The biological function of full-length amyloid-beta protein precursor (AbetaPP), the precursor of Abeta, is not fully understood. Multiple laboratories have reported that antibody binding to cell surface AbetaPP causes neuronal cell death. Here we examined whether induced dimerization of the cytoplasmic domain of AbetaPP (AbetaPPCD) triggers neuronal cell death. In neurohybrid cells expressing fusion constructs of the epidermal growth factor (EGF) receptor with AbetaPPCD (EGFR/AbetaPP hybrids), EGF drastically enhanced neuronal cell death in a manner sensitive to acetyl-l-aspartyl-l-glutamyl-l-valyl-l-aspartyl-aldehyde (Ac-DEVD-CHO; DEVD), GSH-ethyl ester (GEE), and pertussis toxin (PTX). Dominant-negative apoptosis signal-regulating kinase 1 (ASK1) blocked this neuronal cell death, but not alpha-synuclein-induced cell death. Constitutively active ASK1 (caASK1) caused DEVD/GEE-sensitive cell death in a manner resistant to PTX and sensitive to Humanin, which also suppressed neuronal cell death by EGFR/AbetaPP hybrid. ASK1 formed a complex with AbetaPPCD via JIP-1b, the c-Jun N-terminal kinase (JNK)-interacting protein. EGFR/AbetaPP hybrid-induced and caASK1-induced neuronal cell deaths were specifically blocked by SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one), a specific JNK inhibitor. Combined with our earlier study, these data indicate that dimerization of AbetaPPCD triggers ASK1/JNK-mediated neuronal cell death. We also noticed a potential role of ASK1/JNK in sustaining the activity of this mechanism after initial activation by AbetaPP, which allows for the achievement of cell death by short-term anti-AbetaPP antibody treatment. Understanding the function of AbetaPPCD and its downstream pathway should lead to effective anti-Alzheimer's disease therapeutics.
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PMID:The cytoplasmic domain of Alzheimer's amyloid-beta protein precursor causes sustained apoptosis signal-regulating kinase 1/c-Jun NH2-terminal kinase-mediated neurotoxic signal via dimerization. 1282 23