Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic recept...Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.展开更多
Background: Studies demonstrated the autoantiboies against angiotension II type 1 receptor (AT1-AAs) could induce vascular endothelial dysfunction. Our objective is to investigate the effect of AT1-AAs on atherosclero...Background: Studies demonstrated the autoantiboies against angiotension II type 1 receptor (AT1-AAs) could induce vascular endothelial dysfunction. Our objective is to investigate the effect of AT1-AAs on atherosclerosis. Methods: AT1-AAs were purified from sera of patients with primary hypertension. Thirty-six New Zealand white rabbits were underwent balloon-induced abdominal aortic endothelial injury and fed an atherogenic diet for 6 weeks and were randomly divided into six groups with different drugs for 4 weeks. The levels of AT1-AAs, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in different stage were detected by ELISA. The abdominal aortas of rabbits were stained with hematoxylin and eosin. The expression of matrix metalloproteinases-2 (MMP-2) in aortic tissue was detected by Western blotting. Results: The levels of TNF-α in the eighth week (0.17 ± 0.04, 0.34 ± 0.08) and in the tenth week (0.23 ± 0.04, 0.54 ± 0.11) were significantly higher than that at the beginning of test (0.04 ± 0.03, 0.08 ± 0.02) in the group of AT1-AAs with low-dose and high-dose (P Conclusion: The results showed that the AT1-AAs could aggravate the inflammatory reaction and the plaque formation.展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) tran...Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.展开更多
文摘Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.
文摘Background: Studies demonstrated the autoantiboies against angiotension II type 1 receptor (AT1-AAs) could induce vascular endothelial dysfunction. Our objective is to investigate the effect of AT1-AAs on atherosclerosis. Methods: AT1-AAs were purified from sera of patients with primary hypertension. Thirty-six New Zealand white rabbits were underwent balloon-induced abdominal aortic endothelial injury and fed an atherogenic diet for 6 weeks and were randomly divided into six groups with different drugs for 4 weeks. The levels of AT1-AAs, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in different stage were detected by ELISA. The abdominal aortas of rabbits were stained with hematoxylin and eosin. The expression of matrix metalloproteinases-2 (MMP-2) in aortic tissue was detected by Western blotting. Results: The levels of TNF-α in the eighth week (0.17 ± 0.04, 0.34 ± 0.08) and in the tenth week (0.23 ± 0.04, 0.54 ± 0.11) were significantly higher than that at the beginning of test (0.04 ± 0.03, 0.08 ± 0.02) in the group of AT1-AAs with low-dose and high-dose (P Conclusion: The results showed that the AT1-AAs could aggravate the inflammatory reaction and the plaque formation.
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
基金supported by the Postdoctoral Fellow Foundation of the Science and Technology Committee of Shanghai (No. 98-10)the Natural Science Foundation of Chinese People's Armed Police Force (Nos. WKH2006-5 and WKH2008ZO4), China
文摘Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.
