Thioredoxin-1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in Infarcted Myocardium of Diabetic Rats

Samuel, Samson Mathews; Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; Maulik, Gautam; Sudhakaran, P. R.; Maulik, Nilanjana

doi:10.1161/circulationaha.109.872481

Cited by 104 publications

(89 citation statements)

References 37 publications

(52 reference statements)

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“…Thus, resveratrol increased longevity through its effects on SIRT1 and AKT in an in vivo myocardial stress model, suggesting the common activation mechanisms for AKT and SIRT1. 39 However, prior to our study, there were no data documenting the specific interplay between SIRT2 and AKT. We found that inhibition of NAMPT or SIRT2 induces strong acetylation of AKT, which is a new and exciting finding.…”

Section: Discussionmentioning

confidence: 80%

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells

Liu¹,

Klimenkova²,

Klimiankou³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundInhibitors of nicotinamide phosphoribosyltransferase have recently been validated as therapeutic targets in leukemia, but the mechanism of leukemogenic transformation downstream of this enzyme is unclear. Design and MethodsHere, we evaluated whether nicotinamide phosphoribosyltransferase's effects on aberrant proliferation and survival of myeloid leukemic cells are dependent on sirtuin and delineated the downstream signaling pathways operating during this process. ResultsWe identified significant upregulation of sirtuin 2 and nicotinamide phosphoribosyltransferase levels in primary acute myeloid leukemia blasts compared to in hematopoietic progenitor cells from healthy individuals. Importantly, specific inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 significantly reduced proliferation and induced apoptosis in human acute myeloid leukemia cell lines and primary blasts. Intriguingly, we found that protein kinase B/AKT could be deacetylated by nicotinamide phosphoribosyltransferase and sirtuin 2. The anti-leukemic effects of the inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 were accompanied by acetylation of protein kinase B/AKT with subsequent inhibition by dephosphorylation. This leads to activation of glycogen synthase kinase-3 β via diminished phosphorylation and, ultimately, inactivation of β-catenin by phosphorylation. ConclusionsOur results provide strong evidence that nicotinamide phosphoribosyltransferase and sirtuin 2 participate in the aberrant proliferation and survival of leukemic cells, and suggest that the protein kinase B/AKT/ glycogen synthase kinase-3 β/β-catenin pathway is a target for inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 and, thereby, leukemia cell proliferation.

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Section: Discussionmentioning

confidence: 80%

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells

Liu¹,

Klimenkova²,

Klimiankou³

et al. 2011

Haematologica

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“…Furthermore, Nrf2 blockade was reported to suppress angiogenesis in mouse models in vivo (47). Moreover, the Nrf2 targets, heme oxygenase-1 (26, 34) and thioredoxin (67), were shown to confer pro-angiogenic effects in animal disease models, and Nrf2 activation was shown to confer significant anti-apoptotic effects in endothelial cells (75,76,77,78,91). Furthermore, treatment with a pharmacological activator of Nrf2 (resveratrol) was shown to both increase capillary density (60) and improve neurovascular coupling (73) in the aged brain, which were associated with improved cognitive function (60).…”

Section: Discussionmentioning

confidence: 99%

Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats

Csiszár

Gautam

Sоsnowska

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

133

128

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“…(40) XO is an oxidase that produces reactive oxygen species while SOD, an endogenous scavenger of superoxide, is responsible for destroying free superoxide radicals in the body. In the present study, incubation with 5 g/L Xiaokening for 72 hours reversed XO and SOD expression and activity in the arterioles of STZ-induced diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Xiaokening stimulates endothelial nitric oxide release in diabetic rats

Liu

Wei

et al. 2015

smedj

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INTRODUCTIONDiabetes mellitus is a group of metabolic diseases that is characterised by high blood sugar levels. This occurs either because the body does not produce enough insulin or because cells do not respond to the insulin that is produced. In the past few decades, many studies have shown a clear worldwide increase in the incidence of both type 1 and type 2 diabetes mellitus.(1) Without proper treatment, diabetes mellitus can cause many long-term complications, including cardiovascular disease, chronic renal failure, blindness and nerve damage. Microangiopathy, which is caused by vascular endothelial cell injury and dysfunction, is a fundamental process in diabetes mellitus complications.(2-4) Drug interventions are needed to treat these microvascular complications.Reactive oxygen species (ROS) play a crucial role in the pathogenesis of some diseases (e.g. cancer, cardiovascular disease, diabetes mellitus and infl ammation).(5) The effect of the increased production of free radicals in diabetes mellitus is devastating and well documented.(6-8) Streptozotocin (STZ)-induced diabetic rats are one of the animal models for type 1 diabetes mellitus.(9) In type 1 diabetes mellitus, destruction of the β-cells of the islets of Langerhans causes degranulation or reduction of insulin secretion, but not the total absence of insulin in blood.(10) The cytotoxic action of STZ is associated with the generation of ROS, which causes oxidative tissue damage.(11) There is considerable evidence of the role of altered antioxidant defences (including both nonenzymatic and enzymatic antioxidant systems) and free radicals in the aetiology of diabetes mellitus. (12,13) Many studies have reported that the use of traditional Chinese medicines not only helps to lower serum glucose, but also helps to inhibit the development of diabetic complications. ( 14,15) Our previous research, which was conducted on umbilical vein endothelial cells (ECV-304), found that Xiaokening effectively reduces cellular injury and proliferation inhibition resulting from high glucose serum levels. (16,17) In other words, Xiaokening was found to have protective effects for endothelial cells and the ability to improve cell propagation. These fi ndings indicate that Xiaokening has a positive effect on endothelial cells in vitro. However, there is little information on the effect of Xiaokening on endothelial cells within vessels. As the effect of Xiaokening on diabetic arterioles has not been reported, the aim of the present study was to explore its effect on the mesenteric arteriolar endothelial cell function of diabetic rats and the underlying mechanism. METHODSSTZ and 2,3-diaminonaphthalene (DAN) were purchased from Sigma Chemical Company, MO, USA. The STZ was dissolved in a solution of cold citrate buffer (0.1 M, pH 4.5). The DAN was dissolved in methanol. The STZ and DAN solutions used in the present study were freshly dissolved and shielded from light. Antibody for endothelial nitric oxide synthase (eNOS) was purchased from Santa Cruz Biotechnology, TX, USA....

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Thioredoxin-1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in Infarcted Myocardium of Diabetic Rats

Cited by 104 publications

References 37 publications

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells

Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats

Xiaokening stimulates endothelial nitric oxide release in diabetic rats

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