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991.
Zhan Gao Ana Sierra Zhiyong Zhu Siva Rama Krishna Koganti Ekaterina Subbotina Ankit Maheshwari Mark E. Anderson Leonid V. Zingman Denice M. Hodgson-Zingman 《PloS one》2016,11(3)
The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP) channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD) in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB) model of heart failure is coupled with a 35–40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of CaMKII-dependent downregulation of KATP channel expression as a mechanism for vulnerability to injury in failing hearts points to strategies targeting this interaction for potential preventives or treatments. 相似文献
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多氯联苯对剑尾鱼超氧化物岐化酶活性的影响 总被引:19,自引:2,他引:19
目的 研究多氯联苯 (PCBs)暴露对剑尾鱼 (Xiphophorushelleri)超氧化物歧化酶 (SOD)活性的影响 ,探讨剑尾鱼器官组织内SOD活性变化作为环境风险评价 (ERA)的有效生物学标记的可行性。方法 测定了PCBs对剑尾鱼 30d的半致死浓度 (LC50 ) ;使用浸浴法以 0、2、5 0 μg L三个PCBs浓度为剑尾鱼染毒 ,定量测定了 72h内肝、鳃及卵巢组织中的SOD的活性变化。结果 PCBs对剑尾鱼的 30dLC50 为 1 0 5 80 μg L ;PCBs对剑尾鱼肝脏和卵巢的SOD活性有明显 (P <0 0 1 )的影响。在最初染毒的 1 2h内 ,SOD活性略有上升 ,但随暴露时间延长 ,浓度增加 ,肝和卵巢的SOD活性均呈下降趋势。此外 ,结果还显示肝组织的SOD活性较高于卵巢的SOD活性 ,表明不同器官组织的SOD活性对PCBs胁迫的敏感性存在一定的差异。实验中鳃组织SOD活性在PCBs暴露后其变化不明显 (P >0 0 5 )。结论 表明剑尾鱼肝细胞SOD活性可作为环境风险评价 (ERA)的有效生物学标记 相似文献
995.
Jiang P Ji Q Liu Z Snyder LA Benard LM Margolskee RF Max M 《The Journal of biological chemistry》2004,279(43):45068-45075
A wide variety of chemically diverse compounds taste sweet, including natural sugars such as glucose, fructose, sucrose, and sugar alcohols, small molecule artificial sweeteners such as saccharin and acesulfame K, and proteins such as monellin and thaumatin. Brazzein, like monellin and thaumatin, is a naturally occurring plant protein that humans, apes, and Old World monkeys perceive as tasting sweet but that is not perceived as sweet by other species including New World monkeys, mouse, and rat. It has been shown that heterologous expression of T1R2 plus T1R3 together yields a receptor responsive to many of the above-mentioned sweet tasting ligands. We have determined that the molecular basis for species-specific sensitivity to brazzein sweetness depends on a site within the cysteine-rich region of human T1R3. Other mutations in this region of T1R3 affected receptor activity toward monellin, and in some cases, overall efficacy to multiple sweet compounds, implicating this region as a previously unrecognized important determinant of sweet receptor function. 相似文献
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Transmembrane protein 14A (TMEM14A) is a member of TMEMs. Alterations in TMEMs expression have been identified in several types of cancer, but the expression and function of TMEM14A in ovarian cancer is still unclear. Here, analysis on the expression data of the Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (OV) dataset demonstrated the overexpression of TMEM14A in ovarian cancer tissues compared with normal tissues, which was consistent with our real-time PCR analysis on ovarian cancer and normal tissues collected from 30 patients. In addition, TMEM14A knockdown in two ovarian cancer cell lines, A2780 and HO-8910, reduced cell proliferation, causes cell cycle arrest and suppressed cell invasion. Moreover, silencing of TMEM14A notably repressed G1/S cell cycle transition and cell invasion via down-regulating the expression of cell cycle related proteins (Cyclin D1, Cyclin E and PCNA) and metastasis-related proteins (MMP-2 and MMP-9), respectively. TMEM14A knockdown significantly reduced the phosphorylation status of Smad2 and Smad3, downstream effectors of TGF-β signalling. In summary, these results indicate that TMEM14A has a pro-tumorigenic effect in ovarian cancer cells, suggesting an important role of this protein in ovarian cancer oncogenesis and metastasis. 相似文献
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重庆酸雨区马尾松纯林改造对土壤酸化特征及团聚体稳定性的影响 总被引:1,自引:0,他引:1
马尾松对酸沉降危害极其敏感,生产实践中往往通过林分改造来应对酸沉降危害。为掌握酸雨区马尾松纯林改造对土壤酸化环境的影响及科学指导经营管理,采用空间代替时间的方法,对重庆铁山坪林场的马尾松纯林及其阔叶化改造后的香樟林、木荷林、马尾松×香樟混交林和马尾松×木荷混交林土壤养分、酸化特征及团聚体稳定性进行研究。结果表明:(1)除木荷混交林的腐殖质层土壤有机碳和全氮含量显著增加外,其他森林类型总体均减少(P<0.05);香樟林及其混交林的各层土壤全磷和全钾含量均增加,但木荷林及其混交林均减少(P<0.05)。(2)改造为香樟林及其混交林能显著提高土壤pH值、交换性盐基离子含量和盐基饱和度,降低交换性Al3+含量,但改造为木荷林及其混交林则总体对土壤酸化特征影响不明显(P>0.05)。(3)木荷林及其混交林淀积层的水稳性大团聚体含量增加,香樟林及其混交林则是微团聚体含量增加(P<0.05)。(4)改造对各森林类型腐殖质层和木荷林淋溶层及淀积层的土壤团聚体稳定性均无显著影响,但能增强马尾松混交林和香樟林淋溶层或淀积层的土壤团聚体稳定性(P<0.05)。综合来看,改造能改变土壤酸化环境,但各森林类型的影响不同,改造为香樟林或其混交林的改善效果总体好于木荷林或其混交林。因而对酸雨区马尾松纯林改造,还应根据改造树种特性及林分特征,科学确定相应的改造方法,尤其应注重改造林分的全过程抚育经营,以营造良好的林下环境。 相似文献