Gardenamide A Protects RGC-5 Cells from H₂O₂-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Oxidative Stress* ; Second Messenger Systems*; Antioxidants/*pharmacology ; Iridoids/*pharmacology ; Neuroprotective Agents/*pharmacology ; Retinal Ganglion Cells/*drug effects; Animals ; Cell Line ; Hydrogen Peroxide/toxicity ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Retinal Ganglion Cells/metabolism
    • Abstract:
      Gardenamide A (GA) protects the rat retinal ganglion (RGC-5) cells against cell apoptosis induced by H₂O₂. The protective effect of GA was completely abrogated by the specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the specific protein kinase B (Akt) inhibitor Akt VIII respectively, indicating that the protective mechanism of GA is mediated by the PI3K/Akt signaling pathway. The specific extracellular signal-regulated kinase (ERK1/2) inhibitor PD98059 could not block the neuroprotection of GA. GA attenuated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by H₂O₂. Western blotting showed that GA promoted the phosphorylation of ERK1/2, Akt and endothelial nitric oxide synthase (eNOS), respectively, and effectively reversed the H₂O₂-inhibited phosphorylation of these three proteins. LY294002 completely inhibited the GA-activated phosphorylation of Akt, while only partially inhibiting eNOS. This evidence implies that eNOS may be activated directly by GA. PD98059 attenuated only partially the GA-induced phosphorylation of ERK1/2 with/without the presence of H₂O₂, indicating that GA may activate ERK1/2 directly. All these results put together confirm that GA protects RGC-5 cells from H₂O₂ insults via the activation of PI3K/Akt/eNOS signaling pathway. Whether the ERK1/2 signaling pathway is involved requires further investigations.
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    • Contributed Indexing:
      Keywords: cell apoptosis; gardenamide A; neuroprotection; neurotoxicity; oxidative stress
    • Accession Number:
      0 (Antioxidants)
      0 (Iridoids)
      0 (Neuroprotective Agents)
      0 (gardenamide A)
      BBX060AN9V (Hydrogen Peroxide)
      EC 1.14.13.39 (Nitric Oxide Synthase Type III)
      EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
    • Publication Date:
      Date Created: 20150922 Date Completed: 20160617 Latest Revision: 20240520
    • Publication Date:
      20240520
    • Accession Number:
      PMC4613312
    • Accession Number:
      10.3390/ijms160922350
    • Accession Number:
      26389892