Disease relevance of DIETHYL MALEATE

• We report here that administration of ATP in combination with diethylmaleate and X-rays leads to complete regression of 95% of Ehrlich ascites tumours in mice [1].
• Finally, we show that FLR1 overexpression confers resistance to diamide, diethylmaleate, and menadione but hypersensitivity to H(2)O(2), demonstrating that the Flr1p transporter participates in Yap1p-mediated oxidative stress response in S. cerevisiae [2].
• In contrast, pretreatment with diethylmaleate preferentially enhanced the toxicity caused by 2,6-dimethylacetaminophen and, to a lesser extent, acetaminophen, without measurably affecting the toxicity of 3,5-dimethylacetaminophen [3].
• Twenty-four hours after ischemia GFR was 0.05 +/- 0.02 ml/min in diethylmaleate-treated animals and 0.28 +/- 0.06 ml/min in control animals (P less than 0.005) [4].
• Another experiment demonstrated that when papillomas received repeated topical applications of diethylmaleate, a GSH-depleting agent, tumor progression was enhanced [5].

High impact information on DIETHYL MALEATE

• Experimental animals were depleted of cardiac glutathione to 35% of control levels by intraperitoneal injections of diethylmaleate (DEM) [6].
• In addition, erythrocytes were incubated with RBV, and the effects of dipyridamole (DPD), diethylmaleate (DEM), and glutathione ester (GSHE) were studied in vitro [7].
• This increased susceptibility was reproduced in pair-fed control mitochondria pretreated with diethylmaleate [8].
• When cellular GSH levels were lowered by addition of diethylmaleate (which conjugates GSH), this reduced the viability of endothelial cells cultured under normoxic conditions and greatly augmented reoxygenation injury [9].
• Glutathione levels were depleted by diethylmaleate and restored by N-acetylcysteine. iNOS expression was assessed by Western blot, reverse transcription polymerase chain reaction, nitric oxide (NO) metabolites, and immunohistochemistry [10].

Chemical compound and disease context of DIETHYL MALEATE

• The effects of diethylmaleate (DEM), previously demonstrated to inhibit butylated hydroxyanisole (BHA)-induced forestomach hyperplasia, on BHA promotion of forestomach carcinogenesis in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined [11].
• METHODS: PC-3 and LNCaP prostate cancer cells were heat-shocked and then treated with or without diethyl-maleate, etoposide, cycloheximide, or 3 Gray irradiation [12].
• Thiol depletion by diethylmaleate had a negligible effect on cis-platin toxicity [13].
• Pretreatment of animals with diethylmaleate strikingly increases both the pulmonary alkylation and the lung toxicity of 4-ipomeanol [14].
• Chemical depletion of hepatic glutathione with diethylmaleate did not induce hepatocellular injury but augmented hepatic ischemia/reperfusion-induced SGPT release and promoted lipid peroxidation [15].

Biological context of DIETHYL MALEATE

• The appearance of this FM p21 form is very early, being observed 5 min after exposure to diethylmaleate, long before the already observed accumulation of p21 induced by oxidative stress [16].
• The changes observed differ from those previously reported with other hydrocholeretics, such as diethylmaleate; they are likely related to hepatic biotransformation of VPA, which undergoes beta and omega-oxidation, and glucuronidation [17].
• Following GSH depletion by diethylmaleate, fibroblasts (GM 3492) from a clinically unaffected individual resynthesized GSH at a rate approximately twice that observed in fibroblasts from known heterozygotes (GM 3488 and GM 3489) [18].
• DEM treatment also produced a dose-dependent delay in cell cycle progression, which at low concentrations (0.25 mM) consisted of a G2/M arrest and at higher concentrations (1 mM) also involved G1 and S phase delays [19].
• Further, in vitro studies demonstrated that pretreatment of HUVEC monolayers with DEM prevented both ICAM-1 up-regulation and PMN transendothelial migration [20].

Anatomical context of DIETHYL MALEATE

• Concurrent treatment of the hepatocytes with diethylmaleate to deplete intracellular GSH inhibited EDB-induced unscheduled DNA synthesis [21].
• Chinese hamster ovary (CHO) cells cultured in vitro were continuously exposed to increasing concentrations of diethylmaleate (DEM) [22].
• To test this hypothesis, we examined the influence of colchicine and vinblastine, two microtubule inhibitors, on diethylmaleate-induced bile flow and on the biliary secretion of diethylmaleate, an organic anion whose glutathione conjugates may be secreted into bile through the Golgi apparatus and Golgi-derived vesicles [23].
• At electron microscopy, diethylmaleate had induced distension of the Golgi saccules of the hepatocytes [23].
• To further investigate the mechanism(s) involved in regulation of the MPT, we used diethylmaleate to deplete GSH in HL60 cells and increase mitochondrial reactive oxygen species (ROS) production [24].

Associations of DIETHYL MALEATE with other chemical compounds

• We show that the transcription of FLR1 is induced upon cell treatment with the oxidizing agents diamide, diethylmaleate, hydrogen peroxide, and tert-butyl hydroperoxide, the antimitotic drug benomyl, and the alkylating agent methylmethane sulfonate and that this induction is mediated by Yap1p through the three YREs [2].
• LY-ar cells treated with diethyl maleate (DEM) or diamide, agents that deplete cellular thiols, had increased susceptibility to radiation-induced apoptosis in a manner similar to C/M- medium [25].
• When DPPP-labeled cells and DCFH-DA-labeled cells were treated with NO, H(2)O(2), AAPH, and DEM to compare the formation of hydoperoxides in the membrane and cytosol, distinct patterns of peroxide formation were observed [26].
• Vitamin C inhibits diethylmaleate-induced L-cystine transport in human vascular smooth muscle cells [27].
• We then found that two pro-oxidants with activity on sulfhydryl groups, 1-chloro-2,4-dinitrobenzene (CDNB) and diethyl maleate (DEM), blocked the phosphorylation events induced by 100 microM H(2)O(2) [28].

Gene context of DIETHYL MALEATE

• DEM induced WAF1/CIP1 expression in Saos-2 and T98G cells, both of which lack functional p53 protein [19].
• However, cells with either a deregulated RAS pathway or overexpressing CLN2 failed to grow and arrested as budded cells, indicating that a second DEM-sensitive cell cycle step exists [29].
• DEM does not affect the ability of FAC1 to bind hKeap1 in our assay [30].
• We found that diethyl maleate (DEM), a well known activator of Nrf2, induces one of the small Maf genes, mafG [31].
• DEM treatment did not produce an increase in membrane-associated protein kinase C, but ERK2, a mitogen-activated protein kinase, was phosphorylated in a manner consistent with ERK2 activation [19].

Analytical, diagnostic and therapeutic context of DIETHYL MALEATE

• Rates of GSH depletion in Chinese hamster ovary cells exposed to diethylmaleate were essentially the same, whether measured by relative fluorescence intensity, by flow cytometry or by enzymatic assay on cellular extracts [32].
• Replenishment of intracellular GSH in perfused lungs from diethylmaleate-treated rats was pronounced even at 25 microM GSH in the perfusion medium [33].
• One of these, named Rox3, lights up two mRNA species of approximately 3400 and 3600 bp, significantly increased after treatment with DEM or with other oxidizing agents [34].
• GO/G- and DEM-induced VSMC death occurred by apoptosis characterized by "DNA ladders", condensation of nuclei, positive to in situ nick-end labeling and increases in histone-associated DNA fragmentation [35].
• Chemical depletion of gastric mucosal GSH with diethylmaleate or inhibition of GSH synthesis with buthionine sulfoximine increased mucosal injury in the corpus and also rendered the antral mucosa susceptible to ischemia/reperfusion injury [36].

References