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  • Wiley  (2)
  • Knorr, Maike  (2)
  • 1
    In: The FASEB Journal, Wiley, Vol. 24, No. S1 ( 2010-04)
    Abstract: Pentaerithrityl tetranitrate (PETN) treatment is devoid of nitrate tolerance. In this study we tested whether the beneficial effect is related to the induction of heme oxygenase‐1 or whether PETN may preserve aldehyde dehydrogenase (ALDH‐2) activity in purified enzymatic preparations. Methods/Results Recombinant human ALDH‐2 was overexpressed in E. coli using a plasmid: To generate pET16B‐hALDH2, a bacterial expression plasmid coding for a His‐tagged human ALDH2 protein, the plasmid pT7‐7‐hALDH2 (provided by K.K. Ho and H. Weiner, Purdue University, West Lafayette, USA) was digested with NdeI and HindIII. Purity and activity were tested by SDS‐PAGE with Coomassie staining, Western blotting and HPLC‐based activity assay. Reactive oxygen species (ROS) formation was tested by different methods. Glyceryl trinitrate (GTN) caused a severe concentration‐dependent decrease in enzyme activity; PETN‐incubation had only minor effects. Incubation of purified ALDH‐2 with GTN but PETN lead to generation of a reactive species. Conclusions This study revealed that PETN has intrinsic antioxidative properties and does not trigger ALDH‐2‐dependent ROS formation from the purified enzyme.
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 1468876-1
    detail.hit.zdb_id: 639186-2
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    In: The FASEB Journal, Wiley, Vol. 24, No. S1 ( 2010-04)
    Abstract: Vascular complications in diabetes mellitus (DM) are associated with increased reactive oxygen species (ROS) formation. Therefore we tested, if treatment with PETN, which has been shown to induce the antioxidant enzyme heme oxygenase‐1, improves ROS formation and vascular function in a diabetic rat model. Methods/Results DM was induced by a single i.v. injection of streptozotocin (STZ, 60mg/kg) in male Wistar rats. After 8 weeks of PETN (15mg/kg/d) vs. isosorbid dinitrate (ISDN, 10 mg/kg/d) vs. isosorbide‐5‐mononitrate (ISMN, 75mg/kg/d) treatment, rats were sacrificed. STZ‐treated rats showed an increase in vascular and cardiac ROS production, detected by HPLC. Endothelial function, measured by isometric tension studies, was impaired. PETN therapy improved almost all parameters more efficiently than ISDN, while ISMN had no protective effects. Some rats were treated with insulin (2.5U/d). Insulin normalized all parameters completely proving that STZ‐induced vascular dysfunction depends on hyperglycemia but not on unspecific toxicity of the compound. Conclusion In diabetic rats, PETN showed more pronounced antioxidative effects than ISDN. Insulin normalized all parameters and thereby identified the underlying mechanism of cardiovascular dysfunction in STZ‐induced DM to strictly depend on insulin levels highlighting the importance of this model.
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 1468876-1
    detail.hit.zdb_id: 639186-2
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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