Antihypertensive activity of AMC3, an engineered 11S amaranth globulin expressed in Escherichia coli, in spontaneously hypertensive rats

Medina‐Godoy, Sergio; Rodríguez-Yáñez, Silvia K.; Bobadilla, Norma A; Pérez‐Villalva, Rosalba; Valdez-Ortiz, Rafael; Hong, Enrique; Luna-Suárez, Silvia; Paredes‐López, Octavio; Valdéz-Ortiz, Ángel

doi:10.1016/j.jff.2013.06.001

Cited by 15 publications

(7 citation statements)

References 39 publications

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“…Recently, the in vivo effect of an E. coli-modified amarantin protein, four units of Val-Tyr dipeptides (VY) in tandem, and one of Ile-Pro-Pro tripeptides (IPP) incorporated in the amarantin acidic subunit (AMC3) was evaluated in SHRs in a one-time oral administration experiment. This study showed that enzymatic hydrolysates of AMC3-containing ACEI peptide (4xVY and IPP) sequences had significant in vivo antihypertensive action [138]. The positive reports of amarantin expression in E. coli [136,138,139] along with the sustained expression of amarantin-modified proteins in tobacco [134] and tomato [135] prospect the successful production of ACEI peptide fusion proteins in amaranth.…”

Section: Amaranthmentioning

confidence: 92%

“…This study showed that enzymatic hydrolysates of AMC3-containing ACEI peptide (4xVY and IPP) sequences had significant in vivo antihypertensive action [138]. The positive reports of amarantin expression in E. coli [136,138,139] along with the sustained expression of amarantin-modified proteins in tobacco [134] and tomato [135] prospect the successful production of ACEI peptide fusion proteins in amaranth. Araújo et al [145], (d) and (e) establishment of a cell suspension culture from callus for protein/peptide production [146,147], ( f) lettuce leaf explant co-culture with Agrobacterium, (g) and (h) plant regeneration via shoot organogenesis at PCB lab, (i) lettuce transgenic plants which can be used for oral delivery, (j) and (k) agroinfiltration of lettuce leaf explants according to Negrouk et al [74], and (l) example of a control explant (left) and transient expression of a 35S::GUS(int) cassette in lettuce leaves (right).…”

Section: Amaranthmentioning

confidence: 92%

“…Although amaranth has not been genetically modified to produce ACEI peptides, the feasibility of developing a modified amarantin acidic subunit has been widely assessed [129,[134][135][136][137][138][139]. Recently, the in vivo effect of an E. coli-modified amarantin protein, four units of Val-Tyr dipeptides (VY) in tandem, and one of Ile-Pro-Pro tripeptides (IPP) incorporated in the amarantin acidic subunit (AMC3) was evaluated in SHRs in a one-time oral administration experiment.…”

Section: Amaranthmentioning

confidence: 99%

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Prospects for the Production of Recombinant Therapeutic Proteins and Peptides in Plants: Special Focus on Angiotensin I-Converting Enzyme Inhibitory (ACEI) Peptides

Gomes¹,

Oliveira²,

Vieira³

et al. 2020

Genetic Engineering - A Glimpse of Techniques and Applications

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Molecular pharming is a cost-effective, scalable, and safe system to produce high-quality and biologically active recombinant therapeutic proteins. Thus, plants are emerging alternative platform for the production of pharmaceutically relevant proteins such as vaccines, antibodies, antibody derivatives, and some serumderived proteins. Additionally, plants have also been used to produce bioactive and immunogenic peptides. The efficacy, selectivity, specificity, and low toxicity make them particularly well-suited therapeutic agents for various indications, for instance, cardiovascular and infectious diseases, immunological disorders, and cancer. In the broad range of known bioactive peptides, angiotensin I-converting enzyme inhibitory (ACEI) peptides derived from food proteins have attracted particular attention for their ability to prevent hypertension. So far, several ACEI peptides have been identified in food proteins, mainly in milk, eggs, and plants. The industrial production of ACEI peptides is based on enzymatic proteolysis of whole food proteins, which leads to the release of small bioactive peptides with ACE-inhibitory activity. The problems associated to such procedures, namely, cost and loss of functional properties, have demonstrated the need to develop more straightforward methods to produce ACEI peptides. One viable hypothesis, discussed in this chapter, is to genetically engineer crop plants to produce and deliver antihypertensive peptides.

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Section: Amaranthmentioning

confidence: 92%

Section: Amaranthmentioning

confidence: 92%

Section: Amaranthmentioning

confidence: 99%

See 1 more Smart Citation

Prospects for the Production of Recombinant Therapeutic Proteins and Peptides in Plants: Special Focus on Angiotensin I-Converting Enzyme Inhibitory (ACEI) Peptides

Gomes¹,

Oliveira²,

Vieira³

et al. 2020

Genetic Engineering - A Glimpse of Techniques and Applications

View full text Add to dashboard Cite

show abstract

“…Our research group has studied the ACE inhibiting capacity of amaranth isolates, hydrolysates, sprouts, protein fractions, and synthetic peptides and their gastrointestinal products by means of in vitro, in silico, and in vivo assays, obtaining promising results. − On the other hand, Tovar-Pérez et al analyzed the ACE inhibition capacity of albumins and globulins, while Barba de la Rosa et al characterized the amaranth trypsin-digested glutelin ability to produce nitric oxide (a potent vasodilator) by serine phosphorylation in coronary endothelial cells. Besides, Medina-Godoy et al obtained an engineered amaranth 11S globulin (AMC 3) expressed in E. coli and subjected to gastrointestinal digestion. The effect of this preparation was analyzed on spontaneously hypertensive rats (SHR), and good results were obtained.…”

Section: Introductionmentioning

confidence: 99%

“…14−17 On the other hand, Tovar-Peŕez et al 18 analyzed the ACE inhibition capacity of albumins and globulins, while Barba de la Rosa et al 19 potent vasodilator) by serine phosphorylation in coronary endothelial cells. Besides, Medina-Godoy et al 20 obtained an engineered amaranth 11S globulin (AMC 3) expressed in E. coli and subjected to gastrointestinal digestion. The effect of this preparation was analyzed on spontaneously hypertensive rats (SHR), and good results were obtained.…”

Section: ■ Introductionmentioning

confidence: 99%

In Vitro Modulation of Renin–Angiotensin System Enzymes by Amaranth (Amaranthus hypochondriacus) Protein-Derived Peptides: Alternative Mechanisms Different from ACE Inhibition

Quiroga

Aphalo

Nardo

et al. 2017

J. Agric. Food Chem.

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Among the factors affecting the development of cardiovascular diseases, hypertension is one of the most important. Research done on amaranth proteins has demonstrated their hypotensive capacity in vivo and in vitro; nevertheless, the mechanism underlying this effect remains unclear. The aim of this study was to analyze in vitro the inhibition of peptides derived from an amaranth hydrolysate (AHH) on other RAS enzymes other than ACE. The chymase and renin activities were studied. AHH was not able to inhibit chymase activity, although a dose-response effect was found on renin activity (IC 0.6 mg/mL). To provide an approach to the renin inhibition mechanism, we analyzed AHH renin inhibition kinetics and performed a structural characterization of the peptides involved in the effect in terms of molecular size and hydrophobicity. Results suggest that amaranth peptides exhibit renin competitive inhibition behavior. Renin inhibition potency was directly related to peptide hydrophobicity. RP-HPLC separation of AHH and subsequent analysis of the peptide sequences showed 6 peptides belonging to 11S globulin (that can be grouped into 3 families) that would be responsible for renin inhibition. These results demonstrate that Amaranthus hypochondriacus seeds are an adequate source of peptides with renin inhibitory properties that could be used in functional food formulations.

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Current genetic engineering strategies for the production of antihypertensive ACEI peptides

Gomes

Ferreira

Carvalho

et al. 2020

Biotech & Bioengineering

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Hypertension is a major and highly prevalent risk factor for various diseases. Among the most frequently prescribed antihypertensive first‐line drugs are synthetic angiotensin I‐converting enzyme inhibitors (ACEI). However, since their use in hypertension therapy has been linked to various side effects, interest in the application of food‐derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods such as chemical synthesis or enzymatic hydrolysis of food proteins has been proven troublesome. We here provide an overview of current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome the limitations of ACEIp large‐scale production. Latest advances in ACEIp research and current genetic engineering‐based strategies for heterologous production of ACEIp (and precursors) are also presented. Cloning approaches include tandem repeats of single ACEIp, ACEIp fusion to proteins/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp‐containing modified plant storage proteins. Although bacteria have been privileged ACEIp heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae‐based platforms are now emerging. Besides being generally safer, cost‐effective and scalable, these “pharming” platforms can perform therelevant posttranslational modifications and produce (and eventually deliver) biologically active protein/peptide‐based antihypertensive medicines.

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Antihypertensive activity of AMC3, an engineered 11S amaranth globulin expressed in Escherichia coli, in spontaneously hypertensive rats

Cited by 15 publications

References 39 publications

Prospects for the Production of Recombinant Therapeutic Proteins and Peptides in Plants: Special Focus on Angiotensin I-Converting Enzyme Inhibitory (ACEI) Peptides

Prospects for the Production of Recombinant Therapeutic Proteins and Peptides in Plants: Special Focus on Angiotensin I-Converting Enzyme Inhibitory (ACEI) Peptides

In Vitro Modulation of Renin–Angiotensin System Enzymes by Amaranth (Amaranthus hypochondriacus) Protein-Derived Peptides: Alternative Mechanisms Different from ACE Inhibition

Current genetic engineering strategies for the production of antihypertensive ACEI peptides

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