Mechanisms of adrenomedullin antimicrobial action

Allaker, Robert P.; Grosvenor, Paul W.; McAnerney, David C.; Sheehan, Barry E.; Srikanta, Bakula H.; Pell, Keith; Kapas, S.

doi:10.1016/j.peptides.2005.09.003

Cited by 70 publications

(69 citation statements)

References 16 publications

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“…Indeed, the antibacterial capacities for some of these neuropeptides have been described recently. 8,9 In this report, we show that these endogenous peptides act as potent antitrypanosome agents, showing an unusual trypanolytic mechanism.…”

mentioning

confidence: 63%

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

et al. 2008

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Trypanosoma brucei is the causative agent of African sleeping sickness. Available treatments are ineffective, toxic and susceptible to resistance by the parasite. Here we show that various endogenous neuropeptides act as potent antitrypanosome agents. Neuropeptides exerted their trypanolytic activity through an unusual mechanism that involves peptide uptake by the parasite, disruption of lysosome integrity and cytosolic accumulation of glycolytic enzymes. This promotes an energetic metabolism failure that initiates an autophagic-like cell death. Neuropeptide-based treatment improved clinical signs in a chronic model of trypanosomiasis by reducing the parasite burden in various target organs. Of physiological importance is the fact that hosts respond to trypanosome infection producing neuropeptides as part of their natural innate defense. From a therapeutic point of view, targeting of intracellular compartments by neuropeptides suppose a new promising strategy for the treatment of trypanosomiasis.

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mentioning

confidence: 63%

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

et al. 2008

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“…It acts systemically and in autocrine and paracrine fashion [54,55], exerting or mediating vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects [42,50,[56][57][58]. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress, ADM has in preclinical and animal models been shown to reduce hypoxic pulmonary vascular structural remodeling and fibrosis and to inhibit bronchoconstriction; the molecule also has been shown to stabilize barrier function in the lungs by downregulating pro-inflammatory factors and reactive oxidative species [42,50,51,[59][60][61][62].…”

Section: Adm and Proadmmentioning

confidence: 99%

The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review

Schuetz¹,

Marlowe²,

Müeller

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term allcause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, qualityof-life, or pharmacoeconomic outcomes in patients with COPD.

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“…However, such a reduction is much smaller in AM-treated mice, which might contribute to the suppression of the disease trajectory. AM also exerts potent activity against various bacteria [ 35 , 36 ]-for example, Escherichia coli -and the fact that the AM distribution within the mucosa is very similar to that of the defensin family of proteins [ 36 ] suggests that AM may also help defend against infection. In addition, the gastrointestinal tracts of AM-treated mice contain signifi cantly fewer bacterial anaerobes than those of control mice [ 33 ].…”

Section: Preclinical Pharmacological Effect Of Am In Experimental Modmentioning

confidence: 99%

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Kïtamura

Ashizuka

Inatsu

et al. 2015

Innovative Medicine

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Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action, but it also has a wide range of physiological properties including cardiovascular protection, neovascularization, and the ability to suppress apoptosis. It is constitutively produced by various tissues including the gastrointestinal tract. AM production and secretion can be induced by pro-infl ammatory cytokines such as tumor necrosis factor-α and interleukin-1, as well as by lipopolysaccharide. Conversely, AM causes the downregulation of infl ammatory cytokines in cultured cells and downregulates inflammatory processes in various models of colitis, including those induced by acetic acid and by dextran sulfate sodium. AM works by exerting anti-infl ammatory and antibacterial effects and by stimulating mucosal regeneration and supporting maintenance of the colonic epithelial barrier. The present fi ndings suggest that AM could serve as a novel agent for treating refractory ulcerative colitis.

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Mechanisms of adrenomedullin antimicrobial action

Cited by 70 publications

References 16 publications

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

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