出 处:《Chinese Medical Journal》2011年第22期3738-3745,共8页中华医学杂志(英文版)
基 金:This-work was supported by grants from the Youth Science Foundation of China (No. 81100445), Talents Project of Beijing Health Bureau (No. 2009-2-11) and the Basic and Clinical Research Cooperation Fund of Capital Medical University (No. 11JL54).
摘 要:Background Down syndrome (DS) is the most common form of human aneuploidy, and there is no effective therapy for the chromosomal abnormalities. We aimed to unravel the molecular mechanisms underlying DS and to provide clues to prenatal screening. Methods A series of proteomics-based experiments was conducted using 19 patients with DS fetuses and 17 normal pregnancies. The proteome of placenta was investigated as displayed by two-dimensional difference gel electrophoresis (2D-DIGE), and comparisons were made between placentas that developed under DS and normal pregnancy conditions. Multivariate analysis of the resulting protein patterns revealed DS-specific protein expression. Matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) high-resolution tandem mass spectrometer (MS)-based identification was successful for 12 out of 17 selected protein spots. Results Among those, three proteins involved in the resist of reactive oxygen species (ROS) and neurogenesis were more abundant in the DS placenta (superoxide dismutase 1, endoplasmic reticulum protein 29 and heat shock protein beta-l), while peroxiredoxin-6 involved in cell defense mechanism against ROS was expressed at a higher level in the normal pregnancies. Conclusion Knowledge of the DS placenta proteome emphasizes the role of proteins involved in anti-oxidation during DS, and may form the basis of a potential approach to minimize the incidence of DS in the clinical settina.Background Down syndrome (DS) is the most common form of human aneuploidy, and there is no effective therapy for the chromosomal abnormalities. We aimed to unravel the molecular mechanisms underlying DS and to provide clues to prenatal screening. Methods A series of proteomics-based experiments was conducted using 19 patients with DS fetuses and 17 normal pregnancies. The proteome of placenta was investigated as displayed by two-dimensional difference gel electrophoresis (2D-DIGE), and comparisons were made between placentas that developed under DS and normal pregnancy conditions. Multivariate analysis of the resulting protein patterns revealed DS-specific protein expression. Matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) high-resolution tandem mass spectrometer (MS)-based identification was successful for 12 out of 17 selected protein spots. Results Among those, three proteins involved in the resist of reactive oxygen species (ROS) and neurogenesis were more abundant in the DS placenta (superoxide dismutase 1, endoplasmic reticulum protein 29 and heat shock protein beta-l), while peroxiredoxin-6 involved in cell defense mechanism against ROS was expressed at a higher level in the normal pregnancies. Conclusion Knowledge of the DS placenta proteome emphasizes the role of proteins involved in anti-oxidation during DS, and may form the basis of a potential approach to minimize the incidence of DS in the clinical settina.
关 键 词:Down syndrome PLACENTA proteomics two-dimensional difference gel electrophoresis Matrix-assisted laser desorption/ionization
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