Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation

Yoshioka, Yasuhiro; Kadoi, Hisatsugu; Yamamuro, Akiko; Ishimaru, Yuki; Maeda, Shin

doi:10.1016/j.ejphar.2015.12.041

Cited by 24 publications

(26 citation statements)

References 61 publications

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“…Moreover, GSH is a major intrinsic cofactor for GSH-Px activity. Therefore, GSH is an important indicator when evaluating the body's antioxidant defense system [39,40]. GSH is synthesized by consecutive catalysis of γ-glutamylcysteinesynthetase and GCLC using cysteine, glutamate and glycine.…”

Section: Discussionmentioning

confidence: 99%

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Zhao

Zhang

Luan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Shenxian-shengmai (SXSM) oral liquid, a Chinese patent compound medicine, has been used to treat sinus bradyarrhythmias induced by mild sick sinus syndrome in clinical practice. Myocardial ischemia, in particular in serious or right coronary-related heart diseases, can cause bradyarrhythmias and cardiac dysfunction. Moreover, reperfusion of ischemic myocardium is associated with additional myocardial damage known as myocardial ischemia-reperfusion (I/R) injury. This study was designed to evaluate the effects of SXSM on bradyarrhythmias and cardiac dysfunction induced by myocardial I/R injury, and to explore the underlying mechanisms. Methods: Administration of SXSM to adult male Sprague Dawley (SD) rats was achieved orally by gavage and control rats were given equivalent deionized water every day for 14 days. After the last administration, the heart was connected with the Langendorff perfusion apparatus and both groups were subjected to ischemia for 20 min followed by reperfusion for 40 min to induce myocardial I/R injury. Heart rate (HR), left ventricular developed pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max) were recorded by a physiological signal acquisition system. The heart treated with ischemic preconditioning (IPC) for 3 times at a range of 5 min/time before ischemia served as a positive control group. The hearts without I/R injury served as control group. After reperfusion, superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) activities in the myocardium were determined by appropriate assay kits. Myocardial SOD1 and glutamate cysteine ligase catalytic subunit (GCLC) expression were assessed by western blot analysis. For the in vitro study, SXSM serum was prepared according to the serum pharmacological method and neonatal rat cardiomyocytes were isolated from the heart of new born SD rats. Neonatal rat cardiomyocytes were pretreated with SXSM serum and subjected to H₂O₂ or anoxia/ reoxygenation (A/R) treatment to induce oxidative damage. Cell viability was evaluated using a Cell Counting Kit-8 (CCK8) assay. Levels of reactive oxygen species (ROS), SOD, GSH and GSH-Px in cardiomyocytes were determined by appropriate assay kits. SOD1 and GCLC expression were assessed by western blot analysis. Buthionine-[S, R]-sulfoximine (BSO), a GCLC inhibitor, and SOD1 siRNA were also used for identifying the cardiac protective targets of SXSM. Results: SXSM and ischemic preconditioning (IPC) significantly increased heart rate during myocardial reperfusion and protected cardiac function against myocardial I/R injury, including an increase in left ventricular diastolic pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max). We also found that SXSM and IPC improved the expansion of myocardial interstitium, t...

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Section: Discussionmentioning

confidence: 99%

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Zhao

Zhang

Luan

et al. 2018

Cell Physiol Biochem

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“…H9c2 cells are rat heart myoblasts, and are often used to examine the metabolic activity of the heart [35]. U-251 MG cells are human malignant glioma cells [36]. B16-F10 mouse melanoma cells were maintained to study the BGP-15 effect mechanism [37].…”

Section: Cell Culture Modelsmentioning

confidence: 99%

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

et al. 2020

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BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, diastolic dysfunction, tachycardia, heart failure, and atrial fibrillation, and it can alleviate cardiotoxicity. BGP-15 exhibits chemoprotective properties in different cytostatic therapies, and has also proven to be photoprotective. It can additionally have advantageous effects in mitochondrial-stress-related diseases. Although the precise mechanism of the effect is still unknown to us, we know that the molecule is a PARP inhibitor, chaperone co-inducer, reduces ROS production, and is able to remodel the organization of cholesterol-rich membrane domains. In the following review, our aim was to summarize the investigated molecular mechanisms and pharmacological effects of this potential API. The main objective was to present the wide pharmacological potentials of this chemical agent.

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“…Rice is widely consumed around the world and rice-derived peptides are reported to have various biological effects such as anti-microbial activity, (8,9) anti-oxidative activity (10,11) and dipeptidyl peptidase-IV-inhibitory activity. (12,13) Compounds that have so far been reported to increase intracellular glutathione levels include silymarin, (14) cyanohydroxybutene, (15) α-naphthoflavone, (16) apocynin, (17) epalrestat, (18,19) ribose-cysteine, (20) β-carotene, (21) noradrenaline, (22) and lactacystin. (23) In a previous study, we demonstrated that rice-derived peptides (RP), obtained from commercial rice proteins using a commercial protease from Aspergillus oryzae , inhibit dipeptidyl peptidase-IV.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice

Kawakami

Moritani

Uraji³

et al. 2017

J. Clin. Biochem. Nutr.

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Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of rice peptides on acetaminophen-induced hepatotoxicity in mice. ICR mice were orally administered rice peptides (0, 100 or 500 mg/kg) for seven days, followed by the induction of hepatotoxicity via intraperitoneal injection of acetaminophen (700 mg/kg). Pretreatment with rice peptides significantly prevented increases in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels and protected against hepatic glutathione depletion. The expression of γ-glutamylcysteine synthetase, a key regulatory enzyme in the synthesis of glutathione, was decreased by treatment with acetaminophen, albeit rice peptides treatment recovered its expression compared to that achieved treatment with acetaminophen. In addition, histopathological evaluation of the livers also revealed that rice peptides prevented acetaminophen-induced centrilobular necrosis. These results suggest that rice peptides increased intracellular glutathione levels and could protect against acetaminophen-induced hepatotoxicity in mice.

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Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation

Cited by 24 publications

References 61 publications

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice

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