Homocysteine accelerates senescence and reduces proliferation of endothelial progenitor cells

Zhu, Jiali; Chen, J.Z.; Wang, X.X.; Xie, Xueqin; Sun, Jun‐Hui; Zhang, F.R.

doi:10.1016/j.yjmcc.2006.01.011

Cited by 77 publications

(48 citation statements)

References 20 publications

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“…The reduction of NO generation has been implicated in the induction of senescence in mature endothelial cells (22,31). However, in vitro, NO donors such as sodium nitroprusside do not reduce the onset of EPC senescence induced during prolonged culture (45). These authors demonstrated that cell senescence is independent of NO, which is consistent with our results, as sepiapterin had no effect on the number of senescent EPCs in wild-type mice.…”

Section: Discussionsupporting

confidence: 90%

Mthfrdeficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1

Lemarié¹,

Shbat²,

Marchesi³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionsupporting

confidence: 90%

Mthfrdeficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1

Lemarié¹,

Shbat²,

Marchesi³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Therefore, the notable decrease in the activity of NADPH oxidase and the inhibition of the production of ROS may be due to the activation of Akt. Furthermore, Akt dephosphorylation plays a major role in accelerating the senescence and reducing the proliferation of EPCs that is induced by Hcy [33] . Previous studies have shown that many downstream targets of Akt are involved in cell survival pathways, including (apoptosis signal-regulating kinase l, ASKl), FOXO [18] , NF-κB, and the p38MAPK [34] .…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells

Bao

2010

Acta Pharmacol Sin

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Aim: To investigate the protective effects of atorvastatin on homocysteine (Hcy)-induced dysfunction and apoptosis in endothelial progenitor cells (EPCs) and the possible molecular mechanisms. Methods: EPCs were divided into six groups: Hcy treatment groups (0, 50, and 500 μmol/L) and atorvastatin pretreatment groups (0.1, 1, and 10 μmol/L). EPC proliferation, migration, in vitro vasculogenesis activity, and apoptosis rate were assayed by the MTT assay, modified Boyden chamber assay, in vitro vasculogenesis kit, and AnnexinV-FITC apoptosis detection kit, respectively. The level of reactive oxygen species (ROS) in cells was measured using H 2 DCF-DA as a fluorescence probe. The activity of NADPH oxidase was evaluated with lucigenin-enhanced chemiluminescence. NO in the supernatant was detected by the nitrate reductase assay. The eNOS mRNA expression and p-eNOS, p-Akt, p-p38MAPK protein expression were measured by RT-PCR and Western blotting analysis, respectively. Caspase-3 activity was determined by colorimetric assay. Results: Hcy does-dependently impaired the proliferation, migration and in vitro vasculogenesis capacity of EPCs, induced cell apoptosis, increased ROS accumulation and NADPH oxidase activation, and decreased the secretion of NO compared with the control group (P<0.05 or P<0.01). The detrimental effects of Hcy were attenuated by atorvastatin pretreatment. Furthermore, Hcy caused a significant downregulation of eNOS mRNA, p-eNOS, and p-Akt protein expression as well as an upregulation of p-p38MAPK protein expression and caspase-3 activity. These effects of Hcy on EPCs were reversed by atorvastatin in a does-dependent manner. Conclusion: Atorvastatin inhibited homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells, which may be related to its effects on suppressing oxidative stress, up-regulating Akt/eNOS and down-regulating the p38MAPK/caspase-3 signaling pathway.

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“…Cells (1x10 5 ) were seeded in methylcellulose plates (Methocult GF H4434, Cell Systems) with 100 ng/ml human recombinant VEGF in the presence or absence of MG132. Plates were studied under phase contrast microscopy, and colonies were counted after 2 days of incubation by two independent investigators (20,21).…”

Section: Methodsmentioning

confidence: 99%

Proteasome inhibitor MG132 suppresses number and function of endothelial progenitor cells: Involvement of nitric oxide synthase inhibition

2010

Int J Mol Med

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Abstract. The aim of this study was to determine whether proteasome inhibitor MG132 treatment has any effect on endothelial progenitor cells (EPCs). Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. EPCs were identified as adherent cells double positive for DiLDL-up-take and lectin binding by direct fluorescent demonstrated under a laser scanning confocal microscope. After 7 days in culture, EPCs were stimulated with proteasome inhibitor MG132 in series of final concentrations of 20, 50, 100, 200 nmol/l for 12, 24, 48 h. Cell proliferation and apoptosis were determined, respectively, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V/propidium iodide binding assay. Colony-forming capacity was performed by colony assay. EPCs adhesion and migration were assayed with adhesion assay and transwell migration assay, respectively. The expression of endothelial nitric oxide synthase (eNOS) was assayed by Western blot analysis, while nitric oxide (NO) generation was detected using the Griess method. It was found that proteasome inhibitor MG132 decreased the number of EPCs and EPC colonies, increased EPC apoptosis, decreased EPC proliferative, adhesive, migration capacity and eNOS/ NO production in a concentration-and time-dependent manner. These data indicate that proteasome inhibitor MG132 suppresses the number and function of EPCs, and these actions may involve decreased eNOS/NO production in the EPCs.

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Homocysteine accelerates senescence and reduces proliferation of endothelial progenitor cells

Cited by 77 publications

References 20 publications

Mthfrdeficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1

Mthfrdeficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1

Atorvastatin inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells

Proteasome inhibitor MG132 suppresses number and function of endothelial progenitor cells: Involvement of nitric oxide synthase inhibition

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