HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Reduced scytonemin isolated from Nostoc commune suppresses LPS/IFNγ-induced NO production in murine macrophage RAW264 cells by inducing hemeoxygenase-1 expression via the Nrf2/ARE pathway.

Abstract
Reduced scytonemin (R-scy) and scytonemin (Scy) isolated from Nostoc commune exhibit anti-tumor and ultraviolet-absorbing properties. In this study, we examined the effects of R-scy and Scy on the induction of nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon-γ (IFNγ) in murine macrophage RAW264 cells. While both R-scy and Scy suppressed LPS/IFNγ-induced NO production, R-scy exhibited a stronger inhibitory effect compared with Scy. To further elucidate the mechanisms underlying the anti-inflammatory effects of R-scy, we examined the changes in the intracellular signaling cascade after LPS/IFNγ stimulation in cells. In addition to the attenuation of LPS/IFNγ-induced upregulation of the inducible isoform of NO synthase, R-scy decreased the activity of nuclear factor-κB, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) after LPS/IFNγ stimulation. R-scy treatment increased heme oxygenase-1 (HO-1) expression by increasing the intracellular levels of reactive oxygen species and thereby activating nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element signaling. The induction of HO-1 by R-scy was inhibited by pretreatment with an antioxidant, N-acetyl-cysteine (NAC), as well as SB203580 and LY294002, inhibitors for p38 MAPK and PI3K/Akt, respectively. Our findings suggest that the anti-inflammatory effects of R-scy could involve both the ROS/PI3K/Akt and the p38 MAPK/Nrf2 signaling pathways.
AuthorsTomohiro Itoh, Mamoru Koketsu, Naoto Yokota, Shota Touho, Masashi Ando, Yasuyuki Tsukamasa
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 69 Pg. 330-8 (Jul 2014) ISSN: 1873-6351 [Electronic] England
PMID24795232 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Indoles
  • Keap1 protein, mouse
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Phenols
  • Reactive Oxygen Species
  • scytonemin
  • Nitric Oxide
  • Interferon-gamma
  • Heme Oxygenase-1
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
Topics
  • Adaptor Proteins, Signal Transducing (metabolism)
  • Animals
  • Antioxidant Response Elements (drug effects)
  • Cell Line (drug effects)
  • Cytoskeletal Proteins (metabolism)
  • Heme Oxygenase-1 (metabolism)
  • Indoles (isolation & purification, pharmacology)
  • Interferon-gamma (metabolism, pharmacology)
  • Lipopolysaccharides (pharmacology)
  • Macrophages (drug effects, metabolism)
  • Mice
  • NF-E2-Related Factor 2 (metabolism)
  • Nitric Oxide (metabolism)
  • Nostoc commune (chemistry)
  • Phenols (isolation & purification, pharmacology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Signal Transduction (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: