Genipin Derivatives Protect RGC-5 from Sodium Nitroprusside-Induced Nitrosative Stress.

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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:
      Iridoids/*pharmacology ; Neuroprotective Agents/*pharmacology ; Nitroprusside/*pharmacology ; Retinal Ganglion Cells/*drug effects ; Signal Transduction/*drug effects; Animals ; Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; Chromones/pharmacology ; Flavonoids/pharmacology ; Gene Expression Regulation ; Iridoids/chemical synthesis ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1/genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism ; Morpholines/pharmacology ; Neuroprotective Agents/chemical synthesis ; Nitric Oxide/antagonists & inhibitors ; Nitric Oxide/chemistry ; Nitric Oxide/pharmacology ; Nitric Oxide Donors/antagonists & inhibitors ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Retinal Ganglion Cells/cytology ; Retinal Ganglion Cells/metabolism
    • Abstract:
      CHR20 and CHR21 are a pair of stable diastereoisomers derived from genipin. These stereoisomers are activators of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). In the rat retinal ganglion (RGC-5) cell model these compounds are non-toxic. Treatment of RGC-5 with 750 μM of sodium nitroprusside (SNP) produces nitrosative stress. Both genipin derivatives, however, protect these cells against SNP-induced apoptic cell death, although CHR21 is significantly more potent than CHR20 in this regard. With Western blotting we showed that the observed neuroprotection is primarily due to the activation of protein kinase B (Akt)/eNOS and extracellular signal-regulated kinase (ERK1/2) signaling pathways. Therefore, LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor) or PD98059 (a MAPK-activating enzyme inhibitor) abrogated the protective effects of CHR20 and CHR21. Altogether, our results show that in our experimental setup neuroprotection by the diasteromeric pair is mediated through the PI3K/Akt/eNOS and ERK1/2 signaling pathways. Further studies are needed to establish the potential of these compounds to prevent ntric oxide (NO)-induced toxicity commonly seen in many neurodegenerative diseases.
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    • Contributed Indexing:
      Keywords: NO neurotoxicity; apoptosis; genipin; neurodegeneration; neuroprotection; nitric oxide synthase
    • Accession Number:
      0 (1-isopropyloxygenipin)
      0 (Chromones)
      0 (Flavonoids)
      0 (Iridoids)
      0 (Morpholines)
      0 (Neuroprotective Agents)
      0 (Nitric Oxide Donors)
      0 (Phosphoinositide-3 Kinase Inhibitors)
      169D1260KM (Nitroprusside)
      31C4KY9ESH (Nitric Oxide)
      31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
      A3V2NE52YG (genipin)
      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)
      SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
    • Publication Date:
      Date Created: 20160123 Date Completed: 20161018 Latest Revision: 20191210
    • Publication Date:
      20231215
    • Accession Number:
      PMC4730358
    • Accession Number:
      10.3390/ijms17010117
    • Accession Number:
      26797604