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Zhi-Gang Huang Hao-Wen Liu Zhen-Zhen Yan Sheng Wang Lu-Yang Wang 《Channels (Austin, Tex.)》2017,11(2):156-166
Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119). Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits. We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels. Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases. 相似文献
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为明确冷驯化处理对异色瓢虫Harmonia axyridis后代生长发育及适合度的影响, 本研究通过两性生命表的制作, 在室内条件下调查了冷处理后其后代发育历期、 成虫产卵前期、 寿命和生殖力以及后代生命表参数。结果表明: 冷驯化使异色瓢虫后代卵的发育历期延长, 幼虫(1-4龄)和蛹的发育历期则缩短; 随着冷驯化时间的延长, 后代体长和体重增量均减小。且完成发育的后代成虫产卵前期延长, 寿命缩短, 生殖力下降。后代生命表参数内禀增长率(r)、 周限增长率(λ)、 净生殖率(R0)和年龄特征存活率(lx)均降低, 但是后代雌虫所占比例却升高。此外, 冷驯化类型对异色瓢虫后代生长发育的影响也不相同。经相同时间(5 d)的低温诱导, 变温诱导的后代成虫寿命比恒定低温诱导的长, 但是生殖力却低; 变温诱导的后代生命表参数(r, λ和R0)均小于恒定低温诱导的, 但是lx却高于恒定低温诱导的。结果说明, 异色瓢虫亲代经历冷驯化, 这种对低温的可塑性反应会延伸到下一代, 而且还能够影响后代的适合度, 这对其在低温下的存活和繁殖具有重要的意义。 相似文献
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Zhen-Zhen Fan Zhao-Ming Ge Hong-Bin Cai Zhi-Yan Liu Pei Liu Hao-Yue Wang 《Molecular biology reports》2014,41(10):6787-6794
Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (?1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C?1562T variant on stroke risk under the T allele versus C allele [OR T vs. C 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR TT+TC vs. CC 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR TT vs. TC+CC 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR TT vs. CC 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR TC vs. CC 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9?1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene–gene and gene–environment interactions, and provide a more convincing explanation for this association. 相似文献
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Ren-Jin Chen Hong-Hua Yuan Teng-Ye Zhang Zhen-Zhen Wang An-kang Hu Lian-Lian Wu Zhang-Ping Yang Yong-Jiang Mao De-Jun Ji Xiao-Rong Zhu 《Molecular neurobiology》2014,50(3):971-978
Heme oxygenase (HO) represents an intrinsic antiinflammatory system based on its ability to inhibit expression of proinflammatory cytokines. The constitutive isoform heme oxygenase-2 (HO-2) has high expression and activity in cerebral microvascular endothelial cells (CMVEC). This study was undertaken to evaluate the role of HO-2 in regulation of TLR4/MyD88-dependent signaling and to study the effect of HO-2 on the expression and secretion of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and Interleukin-6 (IL6) in CMVEC. HO-2 short hairpin RNA (shRNA) and HO-2 overexpression plasmids were used to observe the effect of HO-2 on proinflammatory cytokines in CMVEC in vitro, and the results showed that the messenger RNA (mRNA) and protein levels of TNF-α and IL6 were increased and decreased, respectively, compared with control groups. LPS-stimulated TNF-α and IL6 mRNA and protein were also reduced in CMVEC treated with an inhibitor of TLR4 signaling, CLI-095, or HO-2 overexpression. CLI-095 and HO-2 overexpression both reduced TLR4 expression in CMVEC, and HO-2 shRNA blocked these effects of CLI-095. CLI-095 and HO-2 overexpression potently suppressed TLR4/MyD88-dependent proinflammatory cytokine expression in CMVEC. These results suggest that HO-2 plays an important role in protecting CMVEC against cytokine-mediated inflammation. 相似文献
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Geographic barriers and Quaternary climate changes are two major forces driving the evolution, speciation, and genetic structuring of extant organisms. In this study, we used Pinus armandii and eleven other Asian white pines (subsection Strobus, subgenus Pinus) to explore the influences of geographic factors and Pleistocene climatic oscillations on species in South China, a region known to be centers of plant endemism and biodiversity hotspots. Range-wide patterns of genetic variation were investigated using chloroplast and mitochondrial DNA markers, with extensive sampling throughout the entire range of P. armandii. Both cpDNA and mtDNA revealed that P. armandii exhibits high levels of genetic diversity and significant population differentiation. Three geographically distinct subdivisions corresponding to the Qinling-Daba Mountains (QDM), Himalaya-Hengduan Mountains (HHM) and Yungui Plateau (YGP) were revealed in mainland China by cpDNA. Their break zone was located in the southeastern margin of the Qinghai-Tibetan Plateau (QTP). A series of massive mountains, induced by the QTP uplift, imposed significant geographic barriers to genetic exchange. The disjunct distribution patterns of ancestral haplotypes suggest that a large continuous population of the white pines may have existed from southwest to subtropical China. Repeated range shifts in response to the Pleistocene glaciations led to the isolation and diversification of the subtropical species. The two Taiwanese white pines share a common ancestor with the species in mainland China and obtain their chloroplasts via long-distance pollen dispersal from North Asian pines. Distinct genetic patterns were detected in populations from the Qinling-Daba Mountains, Yungui Plateau, Himalaya-Hengduan Mountains, and subtropical China, indicating significant contributions of geographic factors to the genetic differentiation in white pines. Our study depicts a clear picture of the evolutionary history of Chinese white pines and highlights the heterogeneous contributions of geography and Pleistocene climatic fluctuations to the extremely high plant species diversity and endemism in South China. 相似文献
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Shi-Jun Wang Zhen-Zhen Qiu Fu-Wei Chen An-Li Mao Jun-Chao Bai Ye-Jing Hong Zhong-Pan Zhang Wu-An Zhu Zhi-Wei Zhang Hao Zhou 《Cell death & disease》2022,13(6)
Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) in renal fibrosis. EVs released by bone marrow mesenchymal stem cells (BMSCs) contain miR-181d, which may represent a potential therapy for renal fibrosis. miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), which activates the nuclear factor-kappa B (NF-κB) signaling pathway. Luciferase assays were performed to confirm the relationship between miR-181d and KLF6. Gain- and loss-of-function studies in vivo and in vitro were performed to assess the effect of BMSC-derived EVs (BMSC-EVs), which contained miR-181d, on KLF6, NF-κB, and renal fibrosis. Transforming growth factor-β (TGF-β)-induced renal tubular epithelial HK-2 cells were treated with EVs derived from BMSCs followed by evaluation of collagen type IV α1 (Col4α1), Collagen I and α-smooth muscle actin (α-SMA) as indicators of the extent of renal fibrosis. Renal fibrosis was induced in rats by unilateral ureteral obstruction (UUO) followed by the subsequent analysis of fibrotic markers. BMSC-EVs had higher miR-181d expression. Overexpression of miR-181d correlated with a decrease in KLF6 expression as well as the levels of IκBα phosphorylation, α-SMA, Col4α1, TGF-βR1 and collagen I in HK-2 cells. In vivo, treatment with miR-181d-containing BMSC-derived EVs was able to restrict the progression of fibrosis in UUO-induced rats. Together, BMSC-EVs suppress fibrosis in vitro and in vivo by delivering miR-181d to neighboring cells, where it targets KLF6 and inhibits the NF-κB signaling pathway.Subject terms: Cell biology, Biotechnology 相似文献
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Liu Xianchen Yang Yanyun Liu Zhen-Zhen Chen Hua Fan Fang Jia Cun-Xian 《Sleep and biological rhythms》2017,15(3):207-216
Sleep and Biological Rhythms - Daytime sleepiness is common in adolescents. The daytime sleepiness scales developed for western adolescents may not be applicable to Chinese adolescents. This study... 相似文献
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