一种新的细胞凋亡相关基因——高同型半胱氨酸诱导基因HCY-2的功能初探

目的　探讨高同型半胱氨酸 (HCY)血症引起心血管病和出生性缺陷的作用机制。方法　采用诱导筛选方法克隆高同型半胱氨酸诱导基因 HCY- 2 ,以 Northern印迹分析检测 HCY- 2基因在大鼠不同组织中的表达 ,以免疫组化方法验证 HCY- 2蛋白在大鼠不同组织中的表达。结果　以诱导筛选方法从大鼠血管平滑肌细胞内克隆到一个新的全长 c DNA,即高同型半胱氨酸诱导基因 HCY- 2 ,它编码 142个氨基酸。Northern印迹分析和免疫组化检测表明 ,HCY- 2基因可在大鼠心、肾、脑、肝、肺等组织中广泛表达。在体外 ,将重组 HCY- 2基因转移至内皮细胞中 ,能够引起细胞凋亡和 DNA损伤 ;在体内 ,将 HCY- 2基因转移至鸡胚内 ,则诱发鸡胚细胞凋亡 ,并引起畸形。结论　 HCY- 2基因可能是一种新的凋亡基因 ,高同型半胱氨酸血症可能通过 HCY- 2基因诱发心血管病和出生性畸形。

A novel apoptotic related gene--homocysteine-induced gene HCY-2

Objective To investigate the mechanisms resulting in cardiovascular diseases and birth defect. Methods Induced screening and differential display,Northern blot,and immunohistochemistry assay were applied to clone the homocysteine induced gene HCY 2 and detect the expression of HCY 2 gene respectively. Results A novel HCY induced full length cDNA-HCY 2 which encodes 142 amino acids was obtained from vascular smooth muscle cells of rats.Results of the Northern blot and immunohistochemistry assays suggest that it widely expresses in many kinds of tissues such as heart,kidney,brain,liver,and lung.In vitro,we transferred recombinant HCY 2 gene into endothelial cells and found that it could induce apoptosis and DNA injury.in vivo,HCY 2 gene could induce chicken embryo cells apoptosis and embryo malformation. Conclusions The results indicated that HCY 2 gene might be a novel apoptosis inducing gene and might be involved in the pathogenesis of cardiovascular diseases and birth defects induced by hyperhomocysteinemia.