Zhang Hongliang, Luo Qin, Liu Zhihong, Wang Yong, Zhao Zhihui
Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
Acta Biochim Biophys Sin (Shanghai). 2015 Mar;47(3):156-63. doi: 10.1093/abbs/gmu130. Epub 2015 Jan 28.
Intracellular vesicular transport is shown to be dysfunctional in pulmonary arterial hypertension (PAH). However, the expression of intracellular vesicular transport proteins in PAH remains unclear. To elucidate the possible role of these proteins in the development of PAH, the changes in the expressions of N-ethyl-maleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP), synaptosome-associated membrane protein 23 (SNAP23), type 2 bone morphogenetic receptor (BMPR2), caveolin-1 (cav-1), and endothelial nitric oxide synthase (eNOS) were examined in lung tissues of monocrotaline (MCT)-treated rats by real-time polymerase chain reaction and western blot analysis. In addition, caspase-3, also examined by western blot analysis, was used as an indicator of apoptosis. Our data showed that during the development of PAH, the expressions of NSF, α-SNAP, and SNAP23 were significantly increased before pulmonary arterial pressure started to increase and then significantly decreased after PAH was established. The expressions of BMPR2 and eNOS were similar to those of NSF, α-SNAP, and SNAP23; however, the expression of cav-1 was down-regulated after MCT treatment. Caspase-3 expression was increased after exposure to MCT. In conclusion, the expressions of NSF, α-SNAP, and SNPA23 changed greatly during the onset of PAH, which was accompanied by abnormal expressions of BMPR2, cav-1, and eNOS, as well as an increase in apoptosis. Thus, changes in NSF, α-SNAP, and SNAP23 expressions appear to be mechanistically associated with the development of PAH in MCT-treated rats.
细胞内囊泡运输在肺动脉高压（PAH）中显示功能失调。然而，PAH中细胞内囊泡运输蛋白的表达仍不清楚。为了阐明这些蛋白在PAH发展中的可能作用，通过实时聚合酶链反应和蛋白质印迹分析，检测了用野百合碱（MCT）处理的大鼠肺组织中N - 乙基马来酰亚胺敏感因子（NSF）、α - 可溶性NSF附着蛋白（α - SNAP）、突触体相关膜蛋白23（SNAP23）、2型骨形态发生蛋白受体（BMPR2）、小窝蛋白 - 1（cav - 1）和内皮型一氧化氮合酶（eNOS）的表达变化。此外，通过蛋白质印迹分析检测的半胱天冬酶 - 3用作细胞凋亡的指标。我们的数据表明，在PAH发展过程中，NSF、α - SNAP和SNAP23的表达在肺动脉压开始升高之前显著增加，而在PAH形成后显著降低。BMPR2和eNOS的表达与NSF、α - SNAP和SNAP23相似；然而，MCT处理后cav - 1的表达下调。暴露于MCT后半胱天冬酶 - 3表达增加。总之，在PAH发病过程中，NSF、α - SNAP和SNPA23的表达发生了很大变化，同时伴有BMPR2、cav - 1和eNOS的异常表达以及细胞凋亡增加。因此，NSF、α - SNAP和SNAP23表达的变化似乎在机制上与MCT处理的大鼠PAH的发展相关。
