ABSTRACT
Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70),which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acidL-glutamine, whose production within the skeletal muscle and liberation into the bloodstream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.
Subject(s)
Humans , Male , Female , Aging/metabolism , Chronic Disease , Exercise , Glutamine/deficiency , HSP70 Heat-Shock Proteins/metabolismABSTRACT
Objective To establish an ion chromatography method to determine the content of galactosamine in heparin sodium sample. Methods The content of galactosamine was determined by the ratio of response value of galactosamine and glucosamine.The determination was performed on an Dionex ICS, and the separation was carried out on a Amino acids capture column (30 mm ×3 mm), Series protect column (30 mm × 3 mm)and analytical column CarboPac PA20 (150 mm ×3 mm).The mobile phase was 14 mM potassium hydroxide solution at a flow rate of 0.4 mL/min; the column tempertature was at 30℃; the injection volume was 10μL.Results Glucosamine hydrochloride had good linearity within the range of 1.013 -16.211μg/mL(Y=2.303 4X+0.824 2,r=0.998 3), the average accuracy was 92.7%, and RSD was 3.2%(n=9), the limit of detection was 0.101 3μg/mL, and the limit of quantitation was 0.337 7μg/mL.D-Galactosamine hydrochloride had good linearity within the range of 0.010 2 -0.162 5 g/mL, (Y=31.157X-0.114 4,r=0.999 3).The accuracy was 102.1%, RSD was 2.4%(n=9).The limit of detection was 0.001 0μg/mL, and the limit of quantitation was 0.003 4μg/mL.The determination of galactosamine in 3 batches of heparin sodium raw material was not detected, (0.02 ±2.1)%, (0.03 ±1.5)%, respectively, which were all lower than the limit value (1%) of United States Pharmacopeia regulation.Conclusion The method for the determination of galactosamine in total hexose amine is successfully developed , which could be used as reference for improvement of the quality standard of heparin sodium.
ABSTRACT
Inflammation is a reaction of a living vascularised tissue to an injury. Conventional or synthetic drugs used in the treatment of inflammatory diseases are inadequate, it sometimes have serious side effects. So, number of herbal medicines is recommended for the treatment of inflammation that has no side effects. The present study is aimed to evaluate the anti inflammatory activity of Talinum fruticosum L on formalin induced paw edema in rats as for controlling inflammatory disorders. The objectives of the present study are to carry out phytochemical screening of selected plant drug , to prepare an aqueous extract from Talinum fruticosum L and to screen the in vivo anti inflammatory effect of Talinum fruticosum L. For phytochemical screening, the secondary metabolites like alkaloid, flavonoid, tannin, saponin, quinine were tested using qualitative spot tests. For anti inflammatory activity, wistar albino rats were used and divided into 6 groups and treated accordingly:Normal control, formalin induced group (0.1ml/kg bw), formalin+ Talinum fruticosum L (100mg/kg bw), formalin+ Talinum fruticosum L (200mg/kg bw), formalin+ Talinum fruticosum L (300mg/kg bw), and plant treated (300mg/kg bw).After the experimental period of 15 days, the blood and tissue samples were collected and biochemical parameter and histpathological studies were carried out.The phytochemical screening suggests the standardization, identity, purity and of presence of phytochemicals like saponins, tannins, flavonoids, terpenoids and cardiac glycosides. Oral administration of formalin to the experimental animals produced reduction in the levels of SOD,GSH,GPX ,GR, serum protein and total RBC and Hb. The animals pretreated with Talinum fruticosum L extract at dose levels of 100,200,300mg/kg bw were significantly increased the levels of the above parameters. A significant increase in the length of the paw thickness, in the level of serum enzymes (SGOT, SGPT, ALP, CK) and Lipid peroxide (LPO), in the level of hydroxy proline, hexosamine and leucocytes was noted in the rats induced with formalin, while these levels were normalized by pretreatment with Talinum fruticosum L extract. The histopathological studies of edematous sections of formalin induced rat paw showed loss of cartilage, osteoblast hyperplasia. Talinum fruticosum L treated formalin induced rats showed moderate reduction in the cartilage and osteoblast. From the present observation, it is evidenced that Talinum fruticosum L would be an effective drug for the treatment of inflammatory reactions.
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Objective To investigate the effect of hexosamine biosynthesis pathway on the development of insulin resistance induced by high fat diet.Methods Normal male SD rats were randomly divided into three groups:control(fed with normal chow),high fat(fed with high fat diet for 13 weeks),and rosiglitazone (intragastric administration with rosiglitazone for 5 weeks)groups.After 13 weeks,all the rats were sacrificed,serum and muscle triglycerides(TG),serum total cholesterol(TC),and serum and muscle free fatty acids(FFA) were measured.Insulin sensitivity wss evaluated by insulin sensitivity index(ISI)and glucose infused rat(GIR) with the hyperinsulinemic englycemic clamp technique.The flux of HBP in skeletal muscle was detected with the expression level of glutamine-fructose-6-phosphate transaminase(GFAT)mRNA(RT-PCR),the content of UDPGlcNAc(HPLC)and the level of O-GlcNAc glycosylation in skeletal muscle proteins(Western blot). Results Compared with control group,senlm TG,TC,FFA and muscle TG,FFA levels of high fat group increased(aII P<0.01).both ISI and GIR decreased(both P<0.01),and the leveIs of GFAT mRNA(0.51±0.05 vs 0.18±0.02),UDP-GlcNAc[(6.18±0.86 vs 2.42±0.36)nmol/g],and O-GIcNAc glycosylation of skeletal muscle proteins in high fat group were raised(all P<0.01).In rosiglitazone group,serum and muscle TG.FFA welc deceased(all P<0.01).insulin sensitivity was increased(P<0.05)and the flux of HBP[GFAT mRNA 0.27±0.03,UDP-GIcNAc(2.62±0.32)nmol/g]was reduced(all P<0.05)as compared with high fat group. Conclusions High fat diet-induced insulin resistance in rats is correlated with the increased flux of HBP in skeletaI muscle.which is decreased by rosiglitazone.
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Objective To investigate the role of hexosamine biosynthesis pathway (HBP) in the functionalalterationofmesangialcellstransinfectedwith glucose transporter 1 (GLUT1) gene. Methods Rat mesangial cells were transinfected with the human GLUT1 gene (MCGT1) by retrovirus vector. Mesangial cells transinfected with bacterial ?-galactosidase (MCLacZ) were used as control. Glucose uptake was detected with 2-deoxy-〔 3H〕-D-glucose (2-DG). Cell size, RNA/DNA ratio, protein/DNA ratio and the synthesis of fibronectin were evaluated by flow cytometry. The activity of glutamine: fructose-6-P aminotransferase (GFAT), which is the key enzyme of HBP, was assayed by spectrophotometry. The expression of GFAT gene was analyzed by RT-PCR. Results MCGT1 demonstrated higher 2-DG uptake than MCLacZ 〔(741.0?60.5)dpm/?g protein vs (92.2?9.0)dpm/?g protein,P