دورية أكاديمية

Non-heme iron protein: a potential target of nitric oxide in acute cardiac allograft rejection.

التفاصيل البيبلوغرافية
العنوان: Non-heme iron protein: a potential target of nitric oxide in acute cardiac allograft rejection.
المؤلفون: Pieper GM; Department of Surgery, Division of Transplant Surgery, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. gmpieper@mcw.edu, Halligan NL, Hilton G, Konorev EA, Felix CC, Roza AM, Adams MB, Griffith OW
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2003 Mar 18; Vol. 100 (6), pp. 3125-30. Date of Electronic Publication: 2003 Mar 06.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, P.H.S.
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Graft Rejection/*metabolism , Heart Transplantation/*physiology , Lysine/*analogs & derivatives , Nitric Oxide/*metabolism , Nonheme Iron Proteins/*metabolism, Aconitate Hydratase/metabolism ; Animals ; Cyclosporine/pharmacology ; Electron Spin Resonance Spectroscopy ; Enzyme Inhibitors/pharmacology ; Graft Rejection/drug therapy ; Graft Rejection/etiology ; Heart Transplantation/adverse effects ; Hemeproteins/chemistry ; Hemeproteins/metabolism ; Immunosuppressive Agents/pharmacology ; Lysine/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type II ; Nonheme Iron Proteins/chemistry ; Rats ; Rats, Inbred Lew ; Rats, Inbred WF ; Rats, Sprague-Dawley ; Transplantation, Homologous ; Transplantation, Isogeneic
مستخلص: We examined iron nitrosylation of non-heme protein and enzymatic activity of the Fe-S cluster protein, aconitase, in acute cardiac allograft rejection. Heterotopic transplantation of donor hearts was performed in histocompatibility matched (isografts: Lewis --> Lewis) and mismatched (allografts: Wistar-Furth --> Lewis) rats. On postoperative days (POD) 4-6, Western blot analysis and immunohistochemistry revealed inducible nitric-oxide synthase (iNOS) protein in allografts but not isografts. EPR spectroscopy revealed background signals at g = 2.003 (for semiquinone) and g = 2.02 and g = 1.94 (for Fe-S cluster protein) in isografts and normal hearts. In contrast, in allografts on POD4, a new axial signal at g = 2.04 and g = 2.02 appeared that was attributed to the dinitrosyl-iron complex formed by nitrosylation of non-heme protein. Appearance of this signal occurred at or before significant nitrosylation of heme protein. Iron nitrosylation of non-heme protein was coincidental with decreases in the nonnitrosylated Fe-S cluster signal at g = 1.94. Aconitase enzyme activity was decreased to approximately 50% of that observed in isograft controls by POD4. Treatment with cyclosporine blocked the (i) elevation of plasma nitrate + nitrite, (ii) up-regulation of iNOS protein, (iii) decrease in Fe-S cluster EPR signal, (iv) formation of dinitrosyl-iron complexes, and (v) loss of aconitase enzyme activity. Formation of dinitrosyl-iron complexes and loss of aconitase activity within allografts also was inhibited by treatment of recipients with a selective iNOS inhibitor, l-N(6)-(1-iminoethyl)lysine. This report shows targeting of an important non-heme Fe-S cluster protein in acute solid organ transplant rejection.
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معلومات مُعتمدة: R01 HL064637 United States HL NHLBI NIH HHS; DK 48423 United States DK NIDDK NIH HHS; HL 64637 United States HL NHLBI NIH HHS; RR 01008 United States RR NCRR NIH HHS; R01 DK048423 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Enzyme Inhibitors)
0 (Hemeproteins)
0 (Immunosuppressive Agents)
0 (N(6)-(1-iminoethyl)lysine)
0 (Nonheme Iron Proteins)
31C4KY9ESH (Nitric Oxide)
83HN0GTJ6D (Cyclosporine)
EC 1.14.13.39 (Nitric Oxide Synthase)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.13.39 (Nos2 protein, rat)
EC 4.2.1.3 (Aconitate Hydratase)
K3Z4F929H6 (Lysine)
تواريخ الأحداث: Date Created: 20030308 Date Completed: 20030421 Latest Revision: 20181113
رمز التحديث: 20240627
مُعرف محوري في PubMed: PMC152257
DOI: 10.1073/pnas.0636938100
PMID: 12624190
قاعدة البيانات: MEDLINE
الوصف
تدمد:0027-8424
DOI:10.1073/pnas.0636938100