Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells

Loreto, Silvia Di; Caracciolo, Valentina; Colafarina, Sabrina; Sebastiani, Pierluigi; Gasbarri, Antonella; Amicarelli, Fernanda

doi:10.1016/j.brainres.2004.01.066

Cited by 78 publications

(50 citation statements)

References 49 publications

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“…Previous studies have established the role of MG in AGE formation and cytotoxicity as well as diseases in which these effects are relevant to pathogenesis, such as diabetic complications, cancer, and aging (40)(41)(42)(43)(44). Because supraphysiological levels of MG (100-1,000 μM) induce AGEs, reactive oxygen species, and apoptosis in neurons (21,45,46), these effects have been thought to underlie the role of MG in CNS disorders, including anxiety. For instance, chronic intracerebroventricular administration of MG was reported to reduce anxiety-like behavior, coincident with AGE accumulation (47).…”

Section: Discussionmentioning

confidence: 99%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

131

214

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Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in mice; however, its role in anxiety is controversial, and the underlying mechanism is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels of methylglyoxal (MG), a GABA A receptor agonist. Mice overexpressing Glo1 on a Tg bacterial artificial chromosome displayed increased anxiety-like behavior and reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety-like behavior, while higher doses caused locomotor depression, ataxia, and hypothermia, which are characteristic effects of GABA A receptor activation. Consistent with these data, we found that physiological concentrations of MG selectively activated GABA A receptors in primary neurons. These data indicate that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABA A receptor activation. More broadly, our findings potentially link metabolic state, neuronal inhibitory tone, and behavior. Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders.

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Section: Discussionmentioning

confidence: 99%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

131

214

View full text Add to dashboard Cite

show abstract

“…There is an increasing number of reports which suggest a pathological role of MG in cellular and tissue injury by several mechanisms such as exacerbation of oxidative stress [21,22,23], impairment of endothelial cells [26] and AGE formation [11]. Interestingly, MG administration has been shown to cause microvascular and glomerular damage in animal experiments [27, 33].…”

Section: Discussionmentioning

confidence: 99%

“…These α-oxoaldehydes display high reactivity and readily form AGEs such as N δ -(5-hydro-4-imidazolon-2-yl)ornithine (G-H1), N δ -(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1), N ε -(carboxymethyl)lysine and N ε -(carboxyethyl)lysine [11,17,18,19,20]. Furthermore α-oxoaldehydes reportedly enhance oxidative stress [21,22,23,24,25], cause impairment of endothelial cell survival [26], and induce diabetes-like microvascular changes [27]. Thus, α-oxoaldehydes may be involved in development of comorbidities such as CVD either directly or indirectly via AGEs.…”

Section: Introductionmentioning

confidence: 99%

Plasma α-Oxoaldehyde Levels in Diabetic and Nondiabetic Chronic Kidney Disease Patients

Nakayama

Nakayama²,

Iwabuchi³

et al. 2008

Am J Nephrol

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“…MG and its products, AGEs, are known to be sources of ROS [29][30][31] that cause oxidative stress. Recently, we reported that MG induces the accumulation of ROS, such as superoxide, in BAECs.…”

Section: Discussionmentioning

confidence: 99%

Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

Takahashi

Tatsunami

Oba

et al. 2010

Biological & Pharmaceutical Bulletin

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Methylglyoxal (MG) is a reactive dicarbonyl compound that is formed as a metabolic byproduct of glycolysis. 1,2) MG is found at high levels in the blood of diabetic patients. 3) MG causes nonenzymatic glycation of proteins to yield irreversible advanced glycation end products (AGEs), leading to cross-linking or degradation of proteins. 4) MG has been linked to the development of diabetic complications related to vascular injury. [3][4][5] MG might contribute to not only the development of diabetes but also the pathogenesis of hypertension. 6) MG induces the apoptosis of Schwann cells, 7,8) human monocytic leukemia U937 cells, 9) and human umbilical vein endothelial cells. 10) It is suggested that oxidative stress is involved in MG-induced apoptosis. Oxidative stress resulting from the accumulation of reactive oxygen species (ROS) has been well characterized in diabetic complications. 11,12) MG inactivates antioxidant enzymes, such as glutathione peroxidase and Cu,Zn-superoxide dismutase. 13,14) The dysfunction of antioxidant defense systems may lead to the progression of oxidative stress and finally cell death, such as apoptosis.Reduced glutathione (GSH), the most abundant non-protein thiol antioxidant in cells, is important for protection against oxidative injury. Chronic intake of MG by mice caused the depletion of blood GSH. 15) Intracellular GSH was depleted in Schwann cells incubated with MG. 8) It was also revealed that N-acetyl-L-cysteine, an antioxidant, restored the MG-induced GSH depletion in Schwann cells and prevented apoptosis. In human monocytic leukemia U937 cells, MG-induced apoptosis and oxidative stress were enhanced by DLbuthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH biosynthesis, and partially blocked by N-acetyl-L-cysteine. 9) However, it remains unknown whether BSO or N-acetyl-Lcysteine affects MG-induced apoptosis and oxidative stress in endothelial cells. Recently, we reported that MG induces apoptosis and oxidative stress in bovine aortic endothelial cells (BAECs). 16,17) MG affected GSH levels in BAECs. 17) In this study, we examined the effect of BSO on MG-induced apoptosis and oxidative stress by using BAECs. MATERIALS AND METHODSMaterials MG (40% aqueous solution), BSO, and p-nitrophenyl phosphate were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Fetal bovine serum (FBS) was from Lonza (Walkersville, MD, U.S.A.). Dulbecco's modified Eagle's medium (DMEM), Dulbecco's phosphate-buffered saline (DPBS), phosphate-buffered saline (PBS) at pH 7.4, Lglutamine, penicillin, and streptomycin were from Gibco BRL (Grand Island, NY, U.S.A.). All other chemicals used were of reagent grade.Endothelial Cell Culture BAECs were purchased from Lonza. Cells were obtained at the third passage, transferred to 75 cm 2 filter vent flasks, and grown to 80-90% confluence in DMEM containing 10% FBS, 4 nM L-glutamine, 100 U/ml penicillin, and 100 mg/ml streptomycin, with incubation at 37°C in a humidified atmosphere of 5% CO 2 and 95% air. Cells were passaged by trypsinization and those b...

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Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells

Cited by 78 publications

References 49 publications

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Plasma α-Oxoaldehyde Levels in Diabetic and Nondiabetic Chronic Kidney Disease Patients

Buthionine Sulfoximine Promotes Methylglyoxal-Induced Apoptotic Cell Death and Oxidative Stress in Endothelial Cells

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