L-arginine catabolism is driven mainly towards nitric oxide synthesis in the erythrocytes of patients with type 2 diabetes at first clinical onset

Savu, Octavian; Iosif, Liviu; Bradescu, Ovidiu Marius; Serafinceanu, Cristian; Papacocea, Raluca; Stoian, Irina

doi:10.1177/0004563214531739

Cited by 11 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Arginase I is known to play an important role in the regulation of the immune system and pathological development as it negatively regulates NO synthesis [ 78 , 79 ]. Different cardiovascular disease states are described which exhibit decreased NO availability and increased arginase activity such as hypertension and diabetes [ 47 , 79 – 81 ]. Increased arginase I activity was found in young RBC from type 2 diabetics and activity decreased with increasing cell age.…”

Section: Discussionmentioning

confidence: 99%

“…Arginase, a key enzyme of the urea cycle, is a main regulator and competitor for RBC-NOS activity [ 44 , 45 ] Arginase I is expressed in a variety of cells [ 46 ] including RBC [ 47 ] and increased arginase expression and activity have been described in animal models [ 48 , 49 ] of diabetes mellitus and in diabetic tissue in humans, as well [ 50 ]. Both, arginase I and RBC-NOS compete for their common substrate L-arginine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells

et al. 2015

View full text Add to dashboard Cite

AimTo investigate RBC-NOS dependent NO signaling during in vivo RBC aging in health and disease.MethodRBC from fifteen healthy volunteers (HC) and four patients with type 2 diabetes mellitus (DM) were separated in seven subpopulations by Percoll density gradient centrifugation.ResultsThe proportion of old RBC was significantly higher in DM compared to HC. In both groups, in vivo aging was marked by changes in RBC shape and decreased cell volume. RBC nitrite, as marker for NO, was higher in DM and increased in both HC and DM during aging. RBC deformability was lower in DM and significantly decreased in old compared to young RBC in both HC and DM. RBC-NOS Serine1177 phosphorylation, indicating enzyme activation, increased during aging in both HC and DM. Arginase I activity remained unchanged during aging in HC. In DM, arginase I activity was significantly higher in young RBC compared to HC but decreased during aging. In HC, concentration of L-arginine, the substrate of RBC-NOS and arginase I, significantly dropped from young to old RBC. In DM, L-arginine concentration was significantly higher in young RBC compared to HC and significantly decreased during aging. In blood from healthy subjects, RBC-NOS activation was additionally inhibited by N5-(1-iminoethyl)-L-Ornithine dihydrochloride which decreased RBC nitrite, and impaired RBC deformability of all but the oldest RBC subpopulation.ConclusionThis study first-time showed highest RBC-NOS activation and NO production in old RBC, possibly to counteract the negative impact of cell shrinkage on RBC deformability. This was even more pronounced in DM. It is further suggested that highly produced NO only insufficiently affects cell function of old RBC maybe because of isolated RBC-NOS in old RBC thus decreasing NO bioavailability. Thus, increasing NO availability may improve RBC function and may extend cell life span in old RBC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Some of them show an increased RBC-NOS activation in RBCs from sickle cell anemia patients and a significant increase in cGMP levels within RBCs has also been found as compared to healthy subjects [25,26]. Recently, it was shown that NO production was higher in RBCs from patients with type 2 diabetes than in controls [27]. The decreased RBC arginase activity could be considered a potential mechanism for increased RBC NO production in early diabetes.…”

Section: Introductionmentioning

confidence: 97%

“…The decreased RBC arginase activity could be considered a potential mechanism for increased RBC NO production in early diabetes. Thus, the RBC pool may be a potentially compensatory intravascular compartment for endothelial dysfunction in diabetes [27]. More recently Bizjak et al [28], by a study on age-dependent changes of rheology and enzymatic properties in RBCs, showed highest RBC-NOS activation and NO production in old RBC, suggesting that this is probably required to counteract the negative impact of cell shrinkage on RBC deformability.…”

Section: Introductionmentioning

confidence: 98%

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

et al. 2016

View full text Add to dashboard Cite

Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRDRBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/ Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD-than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMPmembrane transporter) was significantly lower in ESRDRBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRDRBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRDRBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.Keywords End-stage renal disease Á Red blood cells Á Nitric oxide Á cGMP Á Nitric oxide synthase Mario Bonomini, and Assunta Pandolfi have contributed equally to the study.Electronic supplementary material The online version of this article

show abstract

“…It has also been important for immunological surveillance [ 4 , 5 ]. It gets upregulated in vascular abnormalities [ 6 , 7 ], diabetes [ 8 ], hepatocellular carcinoma [ 9 ], cardiovascular diseases [ 10 ], and neuroinflammation [ 11 ]. Other roles of arginase have also been reviewed [ 12 ], showing impact of arginase on biological significance of arginine metabolism associated pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

KCl-Dependent Release of Mitochondrial Membrane-Bound Arginase Appears to Be a Novel Variant of Arginase-II

Mishra

Rajnikant

2016

Scientifica

View full text Add to dashboard Cite

Arginase regulates arginine metabolism, ornithine-urea cycle, and immunological surveillance. Arginase-I is predominant in cytosol, and arginase-II is localised in the mitochondria. A mitochondrial membrane-bound arginase has also been proposed to be adsorbed with outer membrane of mitochondria which gets released by 150 mM potassium chloride (KCl). It is presumed that inclusion of 150 mM KCl in the homogenization medium would not only facilitate release of arginase bound with outer membrane of mitochondria but also affect functional anatomy of mitochondria, mitochondrial enzymes, and proteins. Therefore, it has been intended to characterize KCl-dependent release of mitochondrial membrane-bound arginase from liver of mice. Results provide advancement in the area of arginase biology and suggest that fraction of mitochondrial membrane-bound arginase contains mitochondrial arginase-II and a variant of arginase-II.

show abstract

L-arginine catabolism is driven mainly towards nitric oxide synthesis in the erythrocytes of patients with type 2 diabetes at first clinical onset

Cited by 11 publications

References 45 publications

Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells

Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

KCl-Dependent Release of Mitochondrial Membrane-Bound Arginase Appears to Be a Novel Variant of Arginase-II

Contact Info

Product

Resources

About