Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK

Bao, Xiaomei; Wu, Chunfang; Li, Guoping

doi:10.1016/j.atherosclerosis.2009.11.032

Cited by 70 publications

(68 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…to underphosphorylated p38 in ES cells [25] and also in endothelial cells [44,45], and we found that both p38 phosphorylation and NOX4 transcription are downregulated during low glucose differentiation. Interestingly, Nox4 has been recently reported to reside in the mitochondrion of the kidney cortex, and its expression is sensitive to glucose levels [46].…”

Section: Discussionsupporting

confidence: 52%

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

View full text Add to dashboard Cite

Accumulating evidence points to reactive oxygen species (ROS) as important signaling molecules for cardiomyocyte differentiation in embryonic stem (ES) cells. Given that ES cells are normally maintained and differentiated in medium containing supraphysiological levels of glucose (25 mM), a condition which is known to result in enhanced cellular ROS formation, we questioned whether this high glucose concentration was necessary for cardiomyocyte lineage potential. We show here that ES cells cultured in physiological glucose (5 mM), maintained their general stemness qualities but displayed an altered mitochondrial metabolism, which resulted in decreased ROS production. Furthermore, ES and induced pluripotent stem (iPS) cells differentiated in lower glucose concentrations failed to generate cardiomyocyte structures; an effect mimicked with antioxidant treatments using catalase, N-acetyl cysteine and mitoubiquinone, under high glucose conditions in ES cells. Molecular analysis revealed that ES cells differentiated in 5 mM glucose had reduced expression of the pro-cardiac NOX4 gene and diminished phosphorylation of p38 mitogen-activated protein kinase (MAPK), together with specific changes in the cardiac transcriptional network. These outcomes could be reversed by supplementation of low glucose cultures with ascorbic acid, paradoxically acting as a pro-oxidant. Furthermore, forced expression of an upstream p38 MAPK kinase (MKK6) could bypass the requirement for ROS during differentiation to cardiomyocytes under low glucose conditions, illustrating a key role for p38 in the cardiac differentiation program. Together these data demonstrate that endogenous ROS control is important for cardiomyocyte formation from ES cells, and furthermore that supraphysiological glucose, by supplying ROS, is absolutely required.

show abstract

Section: Discussionsupporting

confidence: 52%

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

View full text Add to dashboard Cite

show abstract

“…This finding was confirmed by our observation that the above three TNF-induced protein expression levels were partly abolished by the inhibitors of p38 and/or ERK1/2. In addition, previous studies have reported that Nox4-derived ROS stimulate MAPK activation 14,37) . This finding is consistent with our results showing that both Nox and NF-κB dase has been implicated to be the major source of ROS generation in the vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…For example, angiotensin-converting enzyme inhibitors, such as temocaprilat, or angiotensin Ⅱ receptor antagonists, such as olmesartan, not only inhibit the NADPH oxidase activity, including the p22phox expression, but also NF-κB activation, which induces the generation of ROS 41,42) . Statins also inhibit the NAPDH oxidase activity 43,44) and the activation of various related downstream signaling pathways, including that of p38 and ERK1/2, in order to produce anti-atherosclerotic effects 14,45) . Moreover, Fig.…”

Section: Discussionmentioning

confidence: 99%

“…MAPKs constitute a family of serine/threonine-specific kinases including ERK, p38 and c-Jun N-terminal kinase (JNK) 12) . In particular, p38 regulates the synthesis of inflammatory mediators at the level of transcription and translation [13][14][15] . On the other hand, ROS can stimulate p38 phosphorylation in a variety of cells, including HUVECs 14,16) .…”

Section: Ldh Gsh and Sod Assaymentioning

confidence: 99%

“…In particular, p38 regulates the synthesis of inflammatory mediators at the level of transcription and translation [13][14][15] . On the other hand, ROS can stimulate p38 phosphorylation in a variety of cells, including HUVECs 14,16) . The NF-κB complex, which usually associates with IκB 17) , is localized in the cytoplasm in unstimulated cells, and its activation plays a core role in the pathogenesis of inflammation 18) .…”

Section: Ldh Gsh and Sod Assaymentioning

confidence: 99%

See 2 more Smart Citations

Luteolin Protects HUVECs from TNF-α-induced Oxidative Stress and Inflammation via its Effects on the Nox4/ROS-NF-κB and MAPK Pathways

Xia

Wang

Jin

et al. 2014

JAT

132

View full text Add to dashboard Cite

Aim: Inflammation and oxidative stress are now recognized to be two important contributing factors to the development of atherosclerosis (AS). NADPH oxidase-4 (Nox4)-derived reactive oxygen species (ROS), NF-κB and MAPK play crucial roles in these processes. Luteolin, a flavone rich in many plants, can interrupt the molecular expression and inhibit the progression of inflammation and oxidative stress. The present study was designed to test whether luteolin inhibits TNF-α-induced inflammation and oxidative stress in human umbilical vein endothelial cells (HUVECs) and identify some of the mechanisms underlying these effects.

show abstract

N‐acetyl‐L‐cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation

et al. 2018

View full text Add to dashboard Cite

Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown. In the current case-control study, we investigated whether the BM EPCs in PT patients differed from those in good graft function patients. Moreover, we evaluated whether N-acetyl-L-cysteine (NAC, a reactive oxygen species [ROS] scavenger) could enhance BM EPCs from PT patients in vitro and in vivo. The PT patients exhibited dysfunctional BM EPCs characterized by high levels of ROS and apoptosis and decreased migration and angiogenesis capabilities. In vitro treatment with NAC improved the quantity and function of the BM EPCs cultivated from the PT patients by downregulating the p38 MAPK pathway and rescued the impaired BM EPCs to support megakaryocytopoiesis. Furthermore, according to the results of a preliminary clinical study, NAC is safe and effective in PT patients. In summary, these results suggested that the reduced and dysfunctional BM EPCs are involved in the occurrence of PT. The defective BM EPCs in the PT patients can be quantitatively and functionally improved by NAC, indicating that NAC is a promising therapeutic approach for PT patients following allo-HSCT.

show abstract

Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK

Cited by 70 publications

References 26 publications

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Luteolin Protects HUVECs from TNF-α-induced Oxidative Stress and Inflammation via its Effects on the Nox4/ROS-NF-κB and MAPK Pathways

N‐acetyl‐L‐cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation

Contact Info

Product

Resources

About