کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8344282 | 1541565 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cystathionine beta-synthase null homocystinuric mice fail to exhibit altered hemostasis or lowering of plasma homocysteine in response to betaine treatment
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کلمات کلیدی
HCUAdoHcyBetaine-homocysteine S-methyltransferaseCGLS-adenosylhomocysteineBHMTAPTTHcyNACAdoMetCBSALTDmgN-acetylcysteine - N-استیل سیستئینAlanine aminotransferase - آلانین آمینوترانسفرازS-adenosylmethionine - اس-ادنوزیل متیونینCoagulation - انعقاد خونBetaine - بتائینtHcy - تیسیdimethylglycine - دی متیل گلیسینactivated partial thromboplastin time - زمان ترومبوپلاستین جزئی فعال شده استprothrombin time - زمان پروترومبینCystathionine beta-synthase - سیستاتونین بتا سنتازCystathionine - سیستاتیونCystathionine gamma-lyase - سیستاتیونین گاما لیازendoplasmic reticulum - شبکه آندوپلاسمی lactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH total homocysteine - هموسیستئین کلHomocystinuria - هموسیستینوریclassical homocystinuria - هموسیستینوری کلاسیکhomocysteine - هوموسیستئین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cystathionine beta-synthase (CBS) deficient homocystinuria is an inherited metabolic defect that if untreated typically results in mental retardation, thromboembolism and a range of connective tissue disturbances. A knockout mouse model has previously been used to investigate pathogenic mechanisms in classical homocystinuria (Watanabe et al., PNAS 92 (1995) 1585-1589). This mouse model exhibits a semi-lethal phenotype and the majority of mice do not survive the early neonatal period. We report here that the birth incidence of cbs (â/â) mice produced from heterozygous crosses is non-Mendelian and not significantly improved by treatment with either the Hcy lowering compound betaine or the cysteine donor N-acetylcysteine. Betaine treatment did improve survival of cbs (â/â) mice and restored fertility to female cbs (â/â) mice but did so without significantly lowering Hcy levels. Surviving cbs (â/â) mice failed to show any alteration in coagulation parameters compared to wild-type controls. Moribund cbs (â/â) mice exhibited severe liver injury and hepatic fibrosis while surviving cbs (â/â) mice although less severely affected, still exhibited a level of severe liver injury that is not found in the human disease. The hepatopathy observed in this model may offer an explanation for the failure of cbs (â/â) mice to respond to betaine or exhibit a hypercoagulative phenotype. We conclude that although this model provides useful data on the biochemical sequelae of classical homocystinuria, it does not successfully recapitulate a number of important features of the human disease and its use for studying mechanisms in homocystinuria should be treated with caution as the hepatopathy produces changes which could influence the results.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 101, Issues 2â3, OctoberâNovember 2010, Pages 163-171
Journal: Molecular Genetics and Metabolism - Volume 101, Issues 2â3, OctoberâNovember 2010, Pages 163-171
نویسندگان
Kenneth N. Maclean, Jakub Sikora, Viktor Kožich, Hua Jiang, Lori S. Greiner, Eva Kraus, Jakub Krijt, Linda S. Crnic, Robert H. Allen, Sally P. Stabler, Milan Elleder, Jan P. Kraus,