Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism

PLoS One. 2015 Nov 13;10(11):e0143004. doi: 10.1371/journal.pone.0143004. eCollection 2015.

Abstract

Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoic Acid / chemistry
  • Biomarkers / metabolism
  • Caffeic Acids / chemistry
  • Cell Line, Tumor
  • Cinnamates / chemistry
  • Coumaric Acids / chemistry
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • GAP-43 Protein / metabolism
  • Linoleic Acid / chemistry
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Neurites / drug effects*
  • Neurites / metabolism*
  • Neuroblastoma / metabolism
  • Oleic Acid / chemistry
  • Phosphorylation
  • Pleurotus / chemistry*
  • Propionates
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Succinic Acid / chemistry
  • Uridine / chemistry*

Substances

  • Biomarkers
  • Caffeic Acids
  • Cinnamates
  • Coumaric Acids
  • Cyclic AMP Response Element-Binding Protein
  • GAP-43 Protein
  • Propionates
  • cinnamic acid
  • Oleic Acid
  • Benzoic Acid
  • Linoleic Acid
  • Succinic Acid
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • p-coumaric acid
  • caffeic acid
  • Uridine

Grant support

This work was funded by the University of Malaya High Impact Research Ministry of Education (MoE) Grants: UM.C/625/1/HIR/MoE/SC/02 and UM.C/625/1/HIR/MOHE/ASH/01, as well as a Postgraduate Research Grant (PV007/2012A) from the Institute of Research Management & Monitoring (IPPP), University of Malaya.