To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern ...To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 un-related asthmatic individuals and 96 healthy controls. β2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial rever-sibility by β2-agonist evaluated. Results (1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 ± 0.3, 1.6 ± 0.8, and 2.1 ± 3.0 μmol/L,P < 0.05). Conclusion β2-AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. β2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.展开更多
Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important ...Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor(β2-AR) by isoproterenol(ISO). We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.展开更多
文摘To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 un-related asthmatic individuals and 96 healthy controls. β2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial rever-sibility by β2-agonist evaluated. Results (1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 ± 0.3, 1.6 ± 0.8, and 2.1 ± 3.0 μmol/L,P < 0.05). Conclusion β2-AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. β2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.
基金supported by the National Basic Research Program of China (2013CB933701)the National Natural Science Foundation of China (81530009, 21127901, 91213305)Chinese Academy of Science
文摘Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor(β2-AR) by isoproterenol(ISO). We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.
