Alteration of the pattern of β-adrenergic desensitization in cultured L6E9 muscle cells infected with Trypanosoma cruzi

Morris, Stephen A.; Tanowitz, Herbert B.; Rowin, Kenneth S.; Wittner, Murray; Bilezikian, John P.

doi:10.1016/0166-6851(84)90115-4

Cited by 10 publications

(4 citation statements)

References 7 publications

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“…The possible functional consequences of this alteration in G proteins remains to be determined, but it is interesting to note that the adenylate cyclase activity of homogenates prepared from infected endothelial cells is essentially equal to that observed in homogenates prepared from uninfected endothelial cells. However, in other studies, we have determined that infection associated changes in the adenylate cyclase activity may only be revealed under specific reaction conditions (Morris et al, 1984(Morris et al, , 1987. We are current1 pursuing the ossibility that associated increase in binding to this protein may be a consequence of alterations in the processing and translation of the stimulatory G protein.…”

Section: Role Of Ecm In the Expression Of Other Infection Associated mentioning

confidence: 96%

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Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression

Morris¹,

Wittner

Weiss

et al. 1990

Journal Cellular Physiology

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Infection of confluent human umbilical vein endothelial cells by the parasite Trypanosoma cruzi results in the appearance of an altered heparan sulfate proteoglycan (HSPG) isolated from the extracellular matrix of infected endothelial cells (ECMi). HSPG from ECMi differed from HSPG obtained from the extracellular matrix of uninfected endothelial cells (ECMu) by virtue of an 8-10-fold increase in sulfation and a different elution pattern using DEAE Sepharose chromatography. Analysis of the HSPG that binds to acidic fibroblast growth factor (aFGF) revealed that infection increased the proportion of HSPG that binds to aFGF by 35%. Heparitinase and alkaline borohydride treatment of aFGF-binding HSPG and chromatographic resolution on Sepharose CL4B column revealed an infection-associated 10-fold increase in sulfation of the GAG side chain with no significant change in the migration of the core protein. In addition, the aFGF binding HSPG isolated from ECMi demonstrated a markedly attenuated synergistic mitogenic activity with aFGF in a cell proliferation assay. All of the infection associated changes in HSPG could be demonstrated in HSPG obtained from uninfected endothelial cell cultures grown on ECMi. Hence, the ECMi is associated with signals capable of modulating the ECM associated metabolism of uninfected endothelial cells. This facility of ECMi was also shown to extend to patterns of Gs protein synthesis as revealed by Western blot analysis. The observation that the ECM produced by infected endothelial cells can direct the synthetic patterns of uninfected endothelial cells in a manner uniquely observed in infected endothelial cells suggests a plausible pathway by which infection of only a few cells can ultimately result in the coordinate responses of neighboring uninfected cells.

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Section: Role Of Ecm In the Expression Of Other Infection Associated mentioning

confidence: 96%

“…Forty-eight hours after plating, endothelial cells were infected with the Tulahuen strain of T. cruzi obtained directly from mice as previously described (Morris et al, 1984).…”

Section: Growth Of Parasites and Infection Of Endothelial Cellsmentioning

confidence: 99%

Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression

Morris¹,

Wittner

Weiss

et al. 1990

Journal Cellular Physiology

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“…In spite of its benefits on patients with non Chagas' disease CHF, there is considerable uncertainty about the potential role of ACE inhibitors in patients with CHF due to Chagas' disease. Captopril , and ACE inhibitors, has been shown to reduce neurohormonal activation and non-lethal arrhymias in a small number of patients with Chagas' heart failure [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

CHARITY: Cha gas car diomyopathy bi soprolol int ervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

Quiros

Morillo

Casas

et al. 2006

Trials

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Background: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Betaadrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy.

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“…Most patients survive the acute phase of the disease asymptomatically; the chronic stage of the disease develops over 20 -30 years and is manifested by cardiovascular, digestive, and autonomic nervous system disorders (3)(4)(5)(6). Several studies have focused on the disease-related loss of function of the autonomic receptors, the ␤-adrenergic and muscarinic cholinergic receptors (mAChR) 1 (5)(6)(7)(8)(9)(10)(11). The paradoxical severe involvement of the heart in the absence of any form of the parasite there has prompted proposals that autoimmune mechanisms participate in the pathogenesis of this cardiac neuromyopathy (12)(13)(14).…”

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confidence: 99%

Desensitization and Sequestration of Human m2 Muscarinic Acetylcholine Receptors by Autoantibodies from Patients with Chagas' Disease

Leirós

Sterin‐Borda

Borda

et al. 1997

Journal of Biological Chemistry

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Chronic Chagas' disease is associated with pathologic changes of the cardiovascular, digestive, and autonomic nervous system, culminating in autonomic denervation and congestive heart failure. Previously, circulating autoantibodies that activate signaling by cardiac muscarinic acetylcholine receptors (mAChRs) have been described. However, it remains unclear whether the chagasic IgGs directly interact with the m2 mAChRs (predominant cardiac subtype), and, if so, whether chronic exposure of the mAChRs to such activating IgGs would result in receptor desensitization. Here we performed studies with purified and reconstituted hm2 mAChRs and demonstrate that IgGs from chagasic serum immunoprecipitated the mAChRs in a manner similar to an anti-m2 mAChR monoclonal antibody tested in parallel. The chagasic antibodies did not directly interact with the ligand binding site, because the binding of radiolabeled antagonist was unchanged by the addition of the chagasic IgG. In intact cells stably expressing the hm2 mAChR, the chagasic IgGs, but not normal IgGs, mimicked the ability of the agonist acetylcholine to induce two effects associated with agonist-induced receptor desensitization: a decrease in affinity for agonist binding to m2 mAChR and sequestration of the hm2 mAChRs from the cell surface. The results demonstrate that the chagasic IgGs can directly interact with and desensitize m2 mAChRs and provide support for the hypothesis of autoimmune mechanisms having a role in the pathogenesis of Chagas' cardioneuromyopathy.

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Alteration of the pattern of β-adrenergic desensitization in cultured L6E9 muscle cells infected with Trypanosoma cruzi

Cited by 10 publications

References 7 publications

Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression

Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression

CHARITY: Cha gas car diomyopathy bi soprolol int ervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

Desensitization and Sequestration of Human m2 Muscarinic Acetylcholine Receptors by Autoantibodies from Patients with Chagas' Disease

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