目的:探讨血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)对骨髓间充质干细胞(mesenchymal stem cells,MSCs)中信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)水平的调节,分析STAT3在AngⅡ诱导MSCs的血管内...
详细信息
目的:探讨血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)对骨髓间充质干细胞(mesenchymal stem cells,MSCs)中信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)水平的调节,分析STAT3在AngⅡ诱导MSCs的血管内皮生长因子(vascular endothelial growth factor,VEGF)表达增加中的作用,研究血管紧张素转化酶(angiotensin convertingenzyme,ACE)与AngⅡ刺激诱导的STAT3磷酸化之间的关系。方法:分离培养大鼠MSCs,以AngⅡ处理细胞,并用针对STAT3的小干扰RNA(STAT3 siRNA)或ACE抑制剂卡多普利提前进行干预。用免疫印迹法(Western blot)检测细胞内STAT3磷酸化和ACE表达水平;用Real-time PCR法检测细胞内VEGF mRNA表达水平;用ELISA法检测培养液中VEGF蛋白水平。结果:①在MSCs中,AngⅡ诱导STAT3的磷酸化水平增加;②STAT3 siRNA明显抑制AngⅡ诱导的VEGF表达和分泌;③卡托普利显著抑制了AngⅡ诱导的STAT3磷酸化。结论:在MSCs中,STAT3参与了AngⅡ诱导的VEGF表达,并且AngⅡ诱导的STAT3具有ACE依赖性。
Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons,to some extent in astrocytes and neuronal stem *** alternative splicing of nNOS mRNA generates 5 isoforms of nNOS,including nNOS-,nNOS-,nNOS-,nNOS...
详细信息
Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons,to some extent in astrocytes and neuronal stem *** alternative splicing of nNOS mRNA generates 5 isoforms of nNOS,including nNOS-,nNOS-,nNOS-,nNOS-and *** of nNOS is inactive,and dimer is the active *** requires tetrahydrobiopterin (BH 4),heme and L-arginine *** of nNOS expression relies largely on cAMP response element-binding protein (CREB) activity,and nNOS activity is regulated by heat shock protein 90 (HSP90)/HSP70,calmodulin (CaM),phosphorylation and dephosphorylation at Ser847 and Ser1412,and the protein inhibitor of nNOS (PIN).There are primarily 9 nNOS-interacting proteins,including post-synaptic density protein 95 (PSD95),clathrin assembly lymphoid leukemia (CALM),calcium/calmodulindependent protein kinase II alpha (CAMKIIA),Disks large homolog 4 (DLG4),DLG2,6-phosphofructokinase,muscle type (PFK-M),carboxy-terminal PDZ ligand of nNOS (CAPON) protein,syntrophin and dynein light chain (LC).Among them,PSD95,CAPON and PFK-M are important nNOS adapter proteins in *** interaction of PSD95 with nNOS controls synapse formation and is implicated in N-methyl-D-aspartic acid-induced neuronal ***-derived NO is implicated in synapse loss-mediated early cognitive/motor deficits in several neuropathological states,and negatively regulates neurogenesis under physiological and pathological conditions.
暂无评论