Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats

Crisóstomo, Joana; Matafome, Paulo; Santos-Silva, Daniela; Rodrigues, Lisa; Sena, Cristina M.; Pereira, Paulo; Seiça, Raquel

doi:10.1016/j.numecd.2013.01.005

Cited by 33 publications

(21 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the energy metabolism and glucose utilisation is compromised in the brain of Alzheimer patients (Hoyer 2004;Mattson 2012), the MG stress is a suitable tool to investigate the protective effects of GLP-1 analogues. Insulin desensitisation also interferes with cell energy metabolism (Engelbrecht et al 2013) and MG induces similar effects (Crisostomo et al 2013;Engelbrecht et al 2013). Insulin desensitisation has been described in brains of patients with Alzheimer's disease .…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Sharma

Jalewa

Hölscher

2013

Journal of Neurochemistry

129

View full text Add to dashboard Cite

Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies.In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dosedependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victozaâ). It is also tested in clinical trials in patients with Alzheimer disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Sharma

Jalewa

Hölscher

2013

Journal of Neurochemistry

129

View full text Add to dashboard Cite

show abstract

“…Advanced glycation end‐product accumulation is also a consequence of increased substrates availability and inefficient detoxification systems. Advanced glycation end‐product accumulation and their interaction with its receptors (RAGE) have an important role in the pathophysiology of diabetic complications in various organs, including the heart .…”

Section: Discussionmentioning

confidence: 99%

“…Our group recently showed that MG‐treated normal rats have MG levels in heart similar to those observed in diabetic rats. Furthermore, MG led to increased apoptotic markers during ischemia, suggesting that it may contribute to a poor outcome after ischemia . Pyridoxamine, a vitamin B6 derivative, is a strong inhibitor of AGE production, which was shown to scavenge MG, to inhibit protein modification, and to reduce AGE formation in several studies .…”

Section: Introductionmentioning

confidence: 99%

Pyridoxamine Reverts Methylglyoxal‐induced Impairment of Survival Pathways During Heart Ischemia

Almeida

Santos-Silva

Rodrigues

et al. 2013

Cardiovascular Therapeutics

View full text Add to dashboard Cite

SUMMARYBackground and aims: Increased levels of advanced glycation end-products (AGE) and their precursors, such as methylglyoxal (MG), in patients with diabetes may account for impaired response to heart ischemia. Pyridoxamine is a derivate of vitamin B6, which has been shown to reduce AGE formation. Our goal was to assess the role of pyridoxamine in protecting from MG-induced impaired heart response to ischemia. Methods: Wistar rats were subjected to MG administration (WM), MG plus pyridoxamine (WMPyr), or no treatment (W). Half of the hearts from each group were submitted to ischemia and the other half were perfused as control. The levels of CEL, Bcl-2, Bax, and total and phosphorylated forms of JNK and Akt were determined. Results: Methylglyoxal led to higher levels of AGE and AGE receptor (RAGE) than in the W group. During ischemia, MG caused an impairment of survival pathways and Bcl-2/Bax ratio, a marker of apoptosis. Pyridoxamine treatment decreased glycation and restored the activation of JNK and Akt during ischemia. These events were followed by levels of Bcl-2/Bax ratio similar to W group. Conclusion: Methylglyoxal-induced AGE accumulation impairs the activation of cell survival pathways during ischemia. Pyridoxamine-induced decrease of glycation inhibited the effects of MG accumulation in the heart, suggesting that it can be of added value to usual diabetic therapy.

show abstract

“…In vivo, it has recently been demonstrated that long-term MGO administration (14 weeks) to normal rats leads to structural changes in the adipose tissue microvasculature, hypoadiponectinaemia and lipolysis. These effects are associated with increased tissue glycation and impaired expression of apoptotic and angiogenic markers, but not with insulin resistance [174,175]. In contrast, shortterm MGO administration (8 weeks) causes much less severe effects, despite the fact that tissue accumulation of CEL takes place [176,177].…”

Section: Obesitymentioning

confidence: 99%

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015

View full text Add to dashboard Cite

The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

show abstract

Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats

Cited by 33 publications

References 30 publications

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

Pyridoxamine Reverts Methylglyoxal‐induced Impairment of Survival Pathways During Heart Ischemia

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

Contact Info

Product

Resources

About