Vaspin prevents methylglyoxal‐induced apoptosis in human vascular endothelial cells by inhibiting reactive oxygen species generation

Phalitakul, Sukanya; Okada, Muneyoshi; Hara, Yukio; Yamawaki, Hideyuki

doi:10.1111/apha.12139

Cited by 74 publications

(55 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the fluorescent probes DCF and DHE, we also detected high levels of hydrogen peroxide and superoxide formation when HUVECs were stimulated prior to the time point (within 1 h) that apoptotic cell death became evident. Our results are in agreement with previous studies showing ROS generation as an important upstream signal molecule in MGO-induced apoptosis [17, 18, 31, 32]. In our experiments, both AGE inhibitors LR-90 and AG suppressed ROS formation and associated mitochondrial-dependent cell death signaling pathway.…”

Section: Discussionsupporting

confidence: 94%

“…Previous studies have shown that MGO can induce apoptosis in human vascular ECs [15–17], and that this cytotoxic effect occurs mainly through induction of reactive oxygen species (ROS) [15, 17–19], although the molecular mechanism underlying this process is not yet fully understood. The aim of this study was to examine whether LR-90, an AGE inhibitor with pleiotropic properties (antioxidant, anti-inflammatory, carbonyl scavenger) [20–23] could exert a cytoprotective effect on the endothelium by inhibiting apoptosis induced by MGO, and to investigate its effects on the various signaling pathways associated with apoptosis, including oxidative stress, MAPK and caspase activation, and mitochondrial-dependent cell death signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

et al. 2014

View full text Add to dashboard Cite

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound known to induce cellular injury and cytoxicity, including apoptosis in vascular cells. Vascular endothelial cell apoptosis has been implicated in the pathophysiology and progression of atherosclerosis. We investigated whether the advanced glycation end-product inhibitor LR-90 could prevent MGO-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). HUVECs were pre-treated with LR-90 and then stimulated with MGO. Cell morphology, cytotoxicity and apoptosis were evaluated by light microscopy, MTT assay, and Annexin V-FITC and propidium iodide double staining, respectively. Levels of Bax, Bcl-2, cytochrome c, mitogen-activated protein kinases (MAPKs) and caspase activities were assessed by Western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. LR-90 dose-dependently prevented MGO-associated HUVEC cytotoxicity and apoptotic biochemical changes such as loss of MMP, increased Bax/Bcl-2 protein ratio, mitochondrial cytochrome c release and activation of caspase-3 and 9. Additionally, LR-90 blocked intracellular ROS formation and MAPK (p44/p42, p38, JNK) activation, though the latter seem to be not directly involved in MGO-induced HUVEC apoptosis. LR-90 prevents MGO-induced HUVEC apoptosis by inhibiting ROS and associated mitochondrial-dependent apoptotic signaling cascades, suggesting that LR-90 possess cytoprotective ability which could be beneficial in prevention of diabetic related-atherosclerosis.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Also, vaspin protects ECs against NEFA-induced apoptosis via activation of PI 3 k/Akt signaling pathway [322]. Consistently, vaspin diminishes methylglyoxal-induced apoptotic activity in ECs by inhibiting caspase-3 activation through inhibition of Nox-mediated ROS generation [323]. Taken [325,326], confirming the anti-inflammatory role of vaspin on ECs.…”

Section: Vaspinmentioning

confidence: 78%

Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells

et al. 2015

View full text Add to dashboard Cite

Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions-either directly or indirectly-leading to ED and CVD.

show abstract

“…In contrast, increase of NOX activity (Lassegue & Clempus 2003) or inactivation of SOD or GPx (Forgione et al 2002, Lob et al 2010) induces oxidative stress causing vascular inflammatory responses. We have previously demonstrated that vaspin prevented apoptosis mediated by methylglyoxal, a metabolite of glucose via the inhibition of NOX activity in vascular endothelial cells (Phalitakul et al 2013). In the present study, we found that vaspin inhibited the accumulation of 4-HNE adducts, an indicator of ROS generation in mesenteric arterial wall of SHR (Fig.…”

Section: Discussionmentioning

confidence: 99%

Vaspin prevents elevation of blood pressure through inhibition of peripheral vascular remodelling in spontaneously hypertensive rats

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

Vaspin prevents methylglyoxal‐induced apoptosis in human vascular endothelial cells by inhibiting reactive oxygen species generation

Abstract: The present results for the first time demonstrate that vaspin inhibits MGO-induced EC apoptosis by preventing caspase-3 activation via the inhibition of NOX-derived ROS generation.

Cited by 74 publications

References 27 publications

LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

LR-90 prevents methylglyoxal-induced oxidative stress and apoptosis in human endothelial cells

Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells

Vaspin prevents elevation of blood pressure through inhibition of peripheral vascular remodelling in spontaneously hypertensive rats

Contact Info

Product

Resources

About