کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244291 | 1209910 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cystathionine β Synthase Deficiency Promotes Oxidative Stress, Fibrosis, and Steatosis in Mice Liver
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کلمات کلیدی
SOD14-hydroxyalkenalMDAS-adenosylhomocysteineHSCsMTHFRTIMP-1BHMTHeme oxygenase-1SAHHcyCBSα-SMAIL-6TGF-β1HO-14-HNESAMGSHDNPH2,4-dinitrophenylhydrazine - 2،4-dinitrophenylhydrazineROS - ROSS-adenosylmethionine - اس-ادنوزیل متیونینα-smooth muscle actin - اکتین عضله آلفا صافinterleukin 6 - اینترلوکین 6tissue inhibitor of metalloproteinase-1 - بازدارنده بافت متالوپروتئیناز-1betaine-homocysteine methyltransferase - بتائین-هموسیستئین متیل ترانسفرازTransforming growth factor-β1 - تبدیل فاکتور رشد β1tumor necrosis factor-α - تومور نکروز عامل αTUNEL - تونلtHcy - تیسیHepatic stellate cells - سلولهای ستارهای کبدیCystathionine β synthase - سیستاتینین بتا سنتازTNF-α - فاکتور نکروز توموری آلفاmalondialdehyde - مالون دی آلدهیدMethylenetetrahydrofolate reductase - متیلن تتراهیدروفولات ردوکتازMethionine synthase - متیونین سنتازwild-type mice - موش های وحشیtotal homocysteine - هموسیستئین کلhomocysteine - هوموسیستئینGlutathione - گلوتاتیونReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Cystathionine β-synthase (CBS) deficiency causes severe hyperhomocysteinemia, which confers diverse clinical manifestations, notably liver disease. To investigate this aspect of hyperhomocysteinemia, we performed a thorough investigation of liver pathology in CBS-deficient mice, a murine model of severe hyperhomocysteinemia. Methods: The degree of liver injury and inflammation was assessed by histologic examination, by measurements of products of lipid peroxidation, and by formation of carbonyl groups on protein as a measure for the occurrence of protein oxidation. Analysis of profibrogenic, proinflammatory factors and cell apoptosis was performed by Western blots, real-time quantitative reverse-transcription polymerase chain reaction, caspase-3 activity, DNA laddering, and TUNEL assay. Results: Histologic evaluation of liver specimens of 8- to 32-week-old CBS-deficient mice showed that CBS-deficient mice develop inflammation, fibrosis, and hepatic steatosis, concomitant with an enhanced expression of tissue inhibitor of metalloproteinase-1, α-smooth muscle actin, pro(α)1 collagen type I, transforming growth factor-β1, and proinflammatory cytokines. Moreover, even if the proapoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated, caspase-3 was not activated, DNA laddering was not detected, and number of positive TUNEL cells was not increased in liver of CBS-deficient mice compared with wild-type mice. Conclusions: The results show that hyperhomocysteinemia in liver of CBS-deficient mice promotes oxidative stress, which may cause mitochondrial damage in association with activation of hepatic stellate cells, leading to liver injury. The absence of caspase-3 activation, DNA fragmentation, and TUNEL-positive cells shows that protective signals may counteract apoptotic signals in liver of CBS-deficient mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 128, Issue 5, May 2005, Pages 1405-1415
Journal: Gastroenterology - Volume 128, Issue 5, May 2005, Pages 1405-1415
نویسندگان
Karine Robert, Johnny Nehmé, Emmanuel Bourdon, Gérard Pivert, Bertrand Friguet, Claude Delcayre, Jean-Maurice Delabar, Nathalie Janel,