L‐arginine as an adjuvant drug in the treatment of sickle cell anaemia

Elias, Darcielle Bruna Dias; Barbosa, Maritza Cavalcante; Rocha, Lilianne Brito da Silva; Dutra, Luana Letícia Alves; Silva, Herivaldo Ferreira da; Martins, Alice Maria Costa; Gonçalves, Raquel

doi:10.1111/bjh.12114

Cited by 22 publications

(16 citation statements)

References 8 publications

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“…Although hydroxyurea nonresponders are rare in childhood, approximately one-third of adults will not respond, making alternative and combination therapies a worthwhile endeavor. A recent report of coadministration of arginine as an NO substrate in a small group of patients in a randomized trial 29 demonstrated an augmented HbF response and highlighted the need for future multiagent trials. A dose-limiting toxicity for hydoxyurea can be myelosuppression.…”

Section: Hbf-inducing Agentsmentioning

confidence: 99%

Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies

Manwani

Frenette

2013

Blood

290

171

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Recurrent and unpredictable episodes of vaso-occlusion are the hallmark of sickle cell disease. Symptomatic management and prevention of these events using the fetal hemoglobin–reactivating agent hydroxyurea are currently the mainstay of treatment. Discoveries over the past 2 decades have highlighted the important contributions of various cellular and soluble participants in the vaso-occlusive cascade. The role of these elements and the opportunities for therapeutic intervention are summarized in this review.

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Section: Hbf-inducing Agentsmentioning

confidence: 99%

Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies

Manwani

Frenette

2013

Blood

290

171

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“…l -Arginine is a kind of semi-essential amino acid and plays a significant role in nitrogen metabolism and ammonia detoxification as an intermediate in the urea cycle in humans [ 1 ]. It is involved in numerous areas of application, such as food flavor, pharmacology and physiology [ 2 , 3 ]. The biosynthesis of l -arginine in bacteria has become a focus of research interest for the past decades on metabolic regulation.…”

Section: Introductionmentioning

confidence: 99%

Effect of Polyhydroxybutyrate (PHB) storage on l-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation

et al. 2016

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BackgroundCorynebacterium crenatum SYPA 5 is the industrial strain for l-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and l-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the l-arginine biosynthesis in C. crenatum SYPA 5.ResultsC. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of l-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L l-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key l-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9–3.0 times compared with the parent strain.ConclusionsAccumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time l-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular l-arginine and intracellular PHB simultaneously. All of these have a potential biotechnological application as a strategy for high-yield l-arginine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0414-x) contains supplementary material, which is available to authorized users.

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“…There was a greater response in fetal Hb levels and reticulocyte count in the group receiving combination therapy versus HU alone. This study suggests that fetal Hb synthesis depends on NO effect on erythroid progenitors [52].…”

Section: Fetal Hemoglobin Inducing Agentsmentioning

confidence: 60%