原创力文档acid sphingomyelinase gene knockout ameliorates hyperhomocysteinemic glomerular injury in mice lacking cystathionine-β-synthase酸性鞘磷脂酶基因敲除小鼠改善hyperhomocysteinemic肾小球损伤缺乏cystathionine-β-synthase.pdfVIP
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acid sphingomyelinase gene knockout ameliorates hyperhomocysteinemic glomerular injury in mice lacking cystathionine-β-synthase酸性鞘磷脂酶基因敲除小鼠改善hyperhomocysteinemic肾小球损伤缺乏cystathionine-β-synthase
Acid Sphingomyelinase Gene Knockout Ameliorates
Hyperhomocysteinemic Glomerular Injury in Mice
Lacking Cystathionine-b-Synthase
Krishna M. Boini, Min Xia, Justine M. Abais, Ming Xu, Cai-xia Li, Pin-Lan Li*
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, United States of America
Abstract
Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced
glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene
produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and
characterized the mice lacking cystathionine b-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/ 2 and Asm+/ 2
mice. Given that the homozygotes of Cbs2/ 2/Asm2/ 2 mice could not survive for 3 weeks. Cbs+/ 2/Asm+/+, Cbs+/ 2/Asm+/ 2
and Cbs+/ 2/Asm2/ 2 as well as their Cbs wild type littermates were used to study the role of Asm2/ 2 under a background of
Cbs+/ 2 with hHcys. HPLC analysis revealed that plasma Hcys level was significantly elevated in Cbs heterozygous (Cbs+/ 2)
mice with different copies of Asm gene compared to Cbs+/+ mice with different Asm gene copies. Cbs+/ 2/Asm+/+ mice had
significantly increased renal Asm activity, ceramide production and O2.2 level compared to Cbs+/+/Asm+/+, while Cbs+/
2/Asm2/ 2 mice showed significantly reduced renal Asm activity, ceramide production and O .2 level due to increased
2
plasma Hcys levels. Confocal microscopy demonstrated that colocalization
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