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Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway.

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  • معلومة اضافية
    • المصدر:
      Publisher: Canadian Science Publishing Country of Publication: Canada NLM ID: 0372712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1205-7541 (Electronic) Linking ISSN: 00084212 NLM ISO Abbreviation: Can J Physiol Pharmacol Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2011- : Ottawa, ON : Canadian Science Publishing
      Original Publication: Ottawa, National Research Council of Canada.
    • الموضوع:
      Abietanes/*pharmacology ; Antioxidants/*pharmacology ; Hepatocytes/*drug effects ; Hydrogen Peroxide/*toxicity ; Oxidants/*toxicity ; Oxidative Stress/*drug effects ; Signal Transduction/*drug effects ; Sirtuin 1/*metabolism; Apoptosis/drug effects ; Cytoprotection ; Dose-Response Relationship, Drug ; Enzyme Activation ; Hep G2 Cells ; Hepatocytes/enzymology ; Hepatocytes/pathology ; Humans ; RNA Interference ; Sirtuin 1/genetics ; Transfection
    • نبذة مختصرة :
      Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5-10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.
    • Contributed Indexing:
      Keywords: HepG2 cells; SIRT1; acide carnosique; carnosic acid; cellules HepG2; espèces réactives d’oxygène; hydrogen peroxide; peroxyde d’hydrogène; reactive oxygen species
    • الرقم المعرف:
      0 (Abietanes)
      0 (Antioxidants)
      0 (Oxidants)
      BBX060AN9V (Hydrogen Peroxide)
      EC 3.5.1.- (SIRT1 protein, human)
      EC 3.5.1.- (Sirtuin 1)
      LI791SXT24 (salvin)
    • الموضوع:
      Date Created: 20150611 Date Completed: 20160503 Latest Revision: 20191210
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.1139/cjpp-2014-0513
    • الرقم المعرف:
      26059423