1.MicroRNA and metabolism regulation.
Ming LI ; Huiqing XIE ; Wu XIONG ; Dan XU ; Ke CAO ; Rui LIU ; Jianda ZHOU ; Chengqun LUO
Journal of Central South University(Medical Sciences) 2013;38(3):318-322
MicroRNAs have been identified as a new class of regulatory molecules that affect many biological functions by interferring the target gene expressions. Latest studies demonstrate that microRNAs can influence many pivotal bio-processes and deeply involve in the metabolism of glucose, lipid and amino acid and biological oxidation. For glucose metabolism, microRNAs are related to insulin secretion, insulin sensitivity, glucose uptake, glycolysis, oxidation and mitochondrial function. For lipid matebolism, microRNAs can regulate the target genes related to lipid biosynthesis, catabolism and transportation. MicroRNAs can influence glutamine catabolism.
Animals
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Glucose
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metabolism
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Glutamine
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metabolism
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Humans
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Insulin
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metabolism
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Insulin Secretion
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Lipid Metabolism
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physiology
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Metabolism
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physiology
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MicroRNAs
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physiology
2.Glutamine and pediatric nutrition.
Chinese Journal of Pediatrics 2004;42(7):544-547
3.Effects of calcium-binding sites in the S2-S3 loop on human and Nematostella vectensis TRPM2 channel gating processes.
Yu-Huan LUO ; Xia-Fei YU ; Cheng MA ; Fan YANG ; Wei YANG
Journal of Zhejiang University. Science. B 2019;20(12):972-982
As a crucial signaling molecule, calcium plays a critical role in many physiological and pathological processes by regulating ion channel activity. Recently, one study resolved the structure of the transient receptor potential melastatin 2 (TRPM2) channel from Nematostella vectensis (nvTRPM2). This identified a calcium-binding site in the S2-S3 loop, while its effect on channel gating remains unclear. Here, we investigated the role of this calcium-binding site in both nvTRPM2 and human TRPM2 (hTRPM2) by mutagenesis and patch-clamp recording. Unlike hTRPM2, nvTRPM2 cannot be activated by calcium alone. Moreover, the inactivation rate of nvTRPM2 was decreased as intracellular calcium concentration was increased. In addition, our results showed that the four key residues in the calcium-binding site of S2-S3 loop have similar effects on the gating processes of nvTRPM2 and hTRPM2. Among them, the mutations at negatively charged residues (glutamate and aspartate) substantially decreased the currents of nvTRPM2 and hTRPM2. This suggests that these sites are essential for calcium-dependent channel gating. For the charge-neutralizing residues (glutamine and asparagine) in the calcium-binding site, our data showed that glutamine mutating to alanine or glutamate did not affect the channel activity, but glutamine mutating to lysine caused loss of function. Asparagine mutating to aspartate still remained functional, while asparagine mutating to alanine or lysine led to little channel activity. These results suggest that the side chain of glutamine has a less contribution to channel gating than does asparagine. However, our data indicated that both glutamine mutating to alanine or glutamate and asparagine mutating to aspartate accelerated the channel inactivation rate, suggesting that the calcium-binding site in the S2-S3 loop is important for calcium-dependent channel inactivation. Taken together, our results uncovered the effect of four key residues in the S2-S3 loop of TRPM2 on the TRPM2 gating process.
Animals
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Asparagine/physiology*
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Binding Sites
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Calcium/metabolism*
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Glutamine/physiology*
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HEK293 Cells
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Humans
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Ion Channel Gating/physiology*
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Sea Anemones
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TRPM Cation Channels/physiology*
5.Effect of glial cell metabolism on respiratory rhythmical discharge activity in neonatal rat medulla oblongata slices.
Fang FANG ; Yong-gang JIAO ; Guo-cai LI ; Zhong-hai WU
Journal of Southern Medical University 2009;29(12):2410-2413
OBJECTIVETo explore the role of glial cell metabolism in the generation and regulation of central respiratory rhythm.
METHODSThe medulla oblongata slices (600-700 microm) containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets retained from 12 neonatal (0-3 days) Sprague-Dawley rats were prepared and perfused with modified Kreb's solution (MKS). Upon recording of respiratory rhythmical discharge activity (RRDA) of the rootlets of the hypoglossal nerve, the brain slices were treated with glial cell metabolism antagonist L-methionine sulfoximine (L-MSO, 50 micromol/L) for 20 min followed by application of glial cell metabolism agonist L-glutamine (L-GLN, 30 micromol/L) for 20 min, or with L-MSO for 20 min with additional L-GLN for 20 min. The changes in the RRDA of the rootlets of the hypoglossal nerve in response to the treatments were recorded.
RESULTSL-MSO prolonged the respiratory cycle (RC) and expiratory time (TE), and reduced the integral amplitude (IA) and the inspiratory time (TI) in the brain slices. L-GLN induced a significant decrease in RC and TE, but IA and TI showed no obvious variations. The effect of L-MSO on the respiratory rhythm was reversed by the application of L-GLN.
CONCLUSIONGlial cell metabolism may play an important role in the modulation of RRDA in neonatal rat brainstem.
Animals ; Animals, Newborn ; Glutamine ; pharmacology ; In Vitro Techniques ; Medulla Oblongata ; metabolism ; physiology ; Methionine Sulfoximine ; pharmacology ; Neuroglia ; metabolism ; Periodicity ; Rats ; Rats, Sprague-Dawley ; Respiration
6.The effect of glutamine on the antioxidation ability in rats after acute exhausting swimming stress.
Wen-bing XU ; Yong-an GUO ; Yu-ee JI
Chinese Journal of Applied Physiology 2006;22(3):369-370
Animals
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Glutamine
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pharmacology
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Kidney
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drug effects
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metabolism
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Liver
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drug effects
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metabolism
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Male
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Malondialdehyde
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metabolism
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Rats
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Rats, Sprague-Dawley
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Serum
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metabolism
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Stress, Physiological
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Swimming
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physiology
7.Effect of glutamine on intestinal mucosal barrier function in rats with acute hepatic injury.
Hui WANG ; Chen-Zhao SONG ; Qing-Hua MENG ; Yi REN ; Fen-Yan ZHANG ; Jing-Jing ZHAO
Chinese Journal of Experimental and Clinical Virology 2009;23(1):53-55
OBJECTIVETo explore the role of glutamine in LPS and D-Gal induced acute hepatic injury.
METHODSA total of 61 Wistar rats were randomly divided into three groups: control group, model group and GLN pretreated group. The animal model was established by LPS and D-Gal intraperitoneal injection. GLN at dose of 1 g/kg was intragastrically administrated for 7 d before intraperitoneal injection. To evaluate the hepatic injury, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were detected by automatic biochemistry analysator. The liver and bowel tissue was observed by lightmicroscope and transmission electron microscope (TEM). The apoptosis of hepatocyte was detected by TUNEL. HPLC-PED was used in the study of intestinal permeability.
RESULTSNo significant differences were noted between ALT, AST, TBIL level, death rate and intestinal permeability (L/M) between model group and GLN pretreated group; In microscope, the confused structure of hepatic injury and inflammatory infiltration were similar between model group and GLN pretreated group. The injury of bowel was not obviously. Compared with the model group, there was better trend in liver and bowel in GLN pretreated group by transmission electron microscope (TEM). The apoptosis index in GLN pretreated group were lower than those in model group.
CONCLUSIONLPS can induce acute liver injury in D-Gal-sensitized rats.Glutamine has't the trend of protecting liver function and intestinal barrier function,decreasing death rates.
Animals ; Apoptosis ; drug effects ; Female ; Glutamine ; administration & dosage ; Injections, Intraperitoneal ; Intestinal Mucosa ; drug effects ; enzymology ; physiology ; Liver ; drug effects ; injuries ; Random Allocation ; Rats ; Rats, Wistar
8.Metabolic alterations in cancer cells and therapeutic implications.
Naima HAMMOUDI ; Kausar Begam Riaz AHMED ; Celia GARCIA-PRIETO ; Peng HUANG
Chinese Journal of Cancer 2011;30(8):508-525
Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.
Antineoplastic Agents
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therapeutic use
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Drug Resistance, Neoplasm
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Genes, Tumor Suppressor
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physiology
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Glutamine
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metabolism
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Glycolysis
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drug effects
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physiology
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Humans
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Mitochondria
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genetics
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metabolism
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Mutation
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Neoplasms
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drug therapy
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metabolism
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pathology
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Neoplastic Stem Cells
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metabolism
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Oncogenes
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physiology
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Oxidative Phosphorylation
9.Experimental study on the glutamine's intervention effect on the opening of permeability transition pore in myocardial mitochondrial membrane.
Chinese Journal of Applied Physiology 2012;28(1):34-37
OBJECTIVETo explore the intervention effect and the possibly mechanism of the glutamine (Gln) on the opening change of the permeability transition pore (PTP) in the myocardial mitochondrial membrane under the overtraining state.
METHODS30 SD rats were randomly divided into 3 groups (n = 10): control group (CG group), overtraining group (OG group) and supplementary (Gln) + overtraining group group). Spectrophotometry was used to test the openness of the permeability transition pore in the myocardial mitochondrial membrane. Electrochemistry was used to test the malondialdehyde (MDA) and the glutathione (GSH) content and the phospholipase A2 (PLA2) activity.
RESULTSOG group compared with the GOG group, the absorbance (A0) and the absorbance change (Delta A) were decreased significantly (P < 0.05). Rh123 fluorescence (F0) intensity was significantly increased (P < 0.05). Rhodamine123 (Rh123) fluorescence change (delta F) was significantly decreased (P < 0.05). Compared with the GOG, the mitochondrial GSH was significantly decreased (P < 0.05), the PLA2 activity and the content of MDA were significantly increased (P <0.05).
CONCLUSIONOvertraining could lead to opening increase of permeability transition pore in the myocardial mitochondrial membrane, after overtraining, the production of the reactive oxygen species (ROS) and PLA2 activity were increased, GSH content was decreased. But added exogenous Gln had a significant intervention effect for these changes.
Animals ; Glutamine ; pharmacology ; Glutathione ; metabolism ; Male ; Mitochondria, Heart ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; metabolism ; Mitochondrial Membranes ; drug effects ; physiology ; Myocardium ; metabolism ; Permeability ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism
10.Research on the mechanism and regulation of overtraining-related the function of neutrophils by the inhibitor of NADPH oxidase and glutamine supplementation.
Chinese Journal of Applied Physiology 2013;29(4):339-344
OBJECTIVETo investigate the method and mechanism for exercise-related immunosuppression via the inhibitor of NADPH oxidase diphenyleneiodonium(DPI) and glutamine supplementation and on the function of neutrophils after overtraining.
METHODSFifty male Wistar rats were randomly divided into five groups: a negative control group (C), an overtraining group (E), an overtraining + DPI intervention group (D), an overtraining+ glutamine supplementation group(G) and combined glutamine + DPI intervention group(DG). After 36 - 40 h from the last training, eight rats were randomly selected from each group, and blood was sampled from the orbital vein. ELISAs were used to measure serum cytokine levels and lipid peroxidation in blood plasma. Flow cytometry was used to measure neutrophil respiratory burst and phagocytosis. The activity of NADPH oxidase was assessed by chemiluminescence and the gene expression of gp91(phox) and p47(phox) of the NADPH-oxidase subunit was checked by Western blot.
RESULTSCompared with group C, the plasma concentrations of NO increased in group G, and the NO, cytokine-induced neutrophil chemoattractant (CINC) concentrations in group DG increased significantly. The respiratory burst and phagocytosis function of neutrophils were decreased in group E, but in group DG were increased when compared with those of group E. After overtraining the expression of gp91(phox) and p47(phox) was up regulated in group E. There were no significant changes in other groups except group DG, in which the expression of gp91(phox) was down regulated. Compared with group E, the expression of gp91(phox) and p47(phox) was up regulated in group D, group G and group DG.
CONCLUSIONThe activation of NADPH oxidase is responsible for the production of superoxide anions, which may be related to the decrease in neutrophil function after over training and is the mechanism of exercise-related immunosuppression. The DPI treatment combined glutamine supplementation can reverse the decrease neutrophils function after overtraining in vitro.
Animals ; Dietary Supplements ; Glutamine ; pharmacology ; Hyperkinesis ; physiopathology ; Male ; Membrane Glycoproteins ; metabolism ; NADPH Oxidase 2 ; NADPH Oxidases ; antagonists & inhibitors ; metabolism ; Neutrophils ; metabolism ; physiology ; Onium Compounds ; pharmacology ; Oxidation-Reduction ; Rats ; Rats, Wistar ; Respiratory Burst ; physiology