目的:观察apelin-13是否通过影响ABCA1蛋白水平从而调节Aβ代谢。方法:1Western blot检测PC-12细胞血管紧张素受体AT1相关的受体蛋白(putative recep tor p rotein related to the angiotensin recep tor AT1,APJ)表达,以确定PC-12细胞...
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目的:观察apelin-13是否通过影响ABCA1蛋白水平从而调节Aβ代谢。方法:1Western blot检测PC-12细胞血管紧张素受体AT1相关的受体蛋白(putative recep tor p rotein related to the angiotensin recep tor AT1,APJ)表达,以确定PC-12细胞存在apelin-13作用受体。2用不同浓度(1、10、100nmol/L)的apelin-13处理PC-12细胞24h及用100nmol/L apelin-13处理细胞24不同时间(12h、24h、48h)后,酶联免疫吸附法(ELISA)检测Aβ1-40及Aβ1-42水平,Western blot免疫印迹法检测APP、BACE1及NEP蛋白水平,根据试剂盒方法检测BACE1及NEP酶活性,RT-PCR检测ABCA1 m RNA水平,Western Blot检测ABCA1蛋白水平,液体闪烁计数法检测细胞内胆固醇的流出。3先使用ABCA1 Si RNA抑制PC-12细胞ABCA1蛋白表达,再使用100nmol/L apelin-13处理PC-12细胞24h,ELISA检测Aβ1-40及Aβ1-42水平,根据试剂盒方法检测BACE1及NEP酶活性。以确定ABCA1在apelin-13对PC-12细胞Aβ代谢影响中所起的作用。结果:1PC-12细胞存在APJ表达。2Apelin-13显著降低PC-12细胞Aβ1-40及Aβ1-42水平,对APP、BACE1及NEP蛋白表达无显著影响,降低BACE1酶活性,增加NEP酶活性,对ABCA1m RNA水平无影响,增加ABCA1蛋白水平,促进胆固醇流出,减少细胞内脂质蓄积。3使用ABCA1 Si RNA抑制PC-12细胞ABCA1蛋白表达后,apelin-13降低PC-12细胞Aβ1-40及Aβ1-42水平的作用显著减弱,其降低BACE1酶活性及增加NEP酶活性的作用显著抑制。结论:Apelin-13通过增加PC-12细胞ABCA1蛋白水平,从而减少Aβ水平。
As a member of the tissue KLK family,KLK8 has been detected in a variety of tissues and biological ***,the role of KLK8 in the fundamental processes in cardiac pathologies has not yet *** the present study,we demonstr...
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As a member of the tissue KLK family,KLK8 has been detected in a variety of tissues and biological ***,the role of KLK8 in the fundamental processes in cardiac pathologies has not yet *** the present study,we demonstrated that KLK8 expression was upregulated in both hypertrophic hearts and hearts subjected to ischemia-reperfusion *** primary isolated neonatal rat cardiomyocytes,KLK8 overexpressionattenuated,while KLK8 knockdown exacerbatedhypoxia/reoxygenation-induced cell *** pharmacological inhibitors and small interference approaches,we found that the protective effects of KLK8 were mediated by kinin B2 *** the other hand,we also found that KLK8 knockdown inhibited PE-induced cardiomyocyte hypertrophy,while KLK8 overexpression promoted cardiomyocyte hypertrophy via a kinin receptor-independent ***,these data demonstrate that KLK8 initiates anti-apoptotic and hypertrophic responses in cardiomycytes,which seemed to be mediated by different signaling pathways.
Rationale:Pulmonary arterial hypertension(PAH)is a malignant disease and the pathological mechanism is *** arterial remodeling is a major pathological change of PAH and Pulmonary artery smooth muscle(PASMCs)phenotype ...
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Rationale:Pulmonary arterial hypertension(PAH)is a malignant disease and the pathological mechanism is *** arterial remodeling is a major pathological change of PAH and Pulmonary artery smooth muscle(PASMCs)phenotype transformation is the start step in ***:We aimed to indentify the effect of cartilage oligomeric matrix protein(COMP),a normal vascular extracellular matrix,on modulation of PASMCs *** and Results:We demonstrated that pulmonary artery pressure increased obviously in COMP-/-mice and COMP expression decreased significantly in PAH model *** overexpression of COMP was associated positively with the expression of PASMCs differentiation marker genes during phenotype ***,knockdown of COMP by small interfering(si)RNA favored ***,knockdown of COMP by si RNA downregulated the expression of BMPRⅡ and overexpression of COMP reversed the ***:Our data suggest that COMP is essential for maintaining a PASMCs contractile phenotype and the protective effects of COMP on PAH may be mediated through BMPRⅡ.Our study will enrich the knowledge of the extracellular matrix on PAH,and investigations to identify the factors affecting the expression and integrity of COMP may provide a novel therapeutic target for PAH.
The mammalian hippocampus is mainly divided into the CA1,CA3,and dentate gyrus(DG),and each subregion has different function in learning and memory *** receives projections from noradrenergic neurons in the locus ce...
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The mammalian hippocampus is mainly divided into the CA1,CA3,and dentate gyrus(DG),and each subregion has different function in learning and memory *** receives projections from noradrenergic neurons in the locus ceruleus,andαas well asβadrenoceptors are expressed in the DG *** has been shown thatα1-adrenoceptors in the CA1 region play an important modulatory role in several learning and memory,but the effect ofα1-adrenoceptors in the hippocampal DG on active avoidance learning have not been ***,in the present study,we used an in vivo brain microdialysis technique to determine norepinephrine(NE)release in the DG during active avoidance conditioned reflex,and then the antagonist or agonist of theα1-adrenoceptors were microinjected into the DG region,and the active avoidance learning was *** concentration of NE in the hippocampal DG was significantly increased in the establishment but not extinction during the active avoidance conditioned *** of prazosin(an antagonist ofα1-adrenoceptors)into the DG facilitated the establishment process but did not affect extinction process in active avoidance ***(an agonist ofα1-adrenoceptors)in the DG inhibited the establishment process and facilitated the extinction *** results suggest that NE in the hippocampal DG inhibits the active avoidance learning viaα1-adrenoceptors.
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