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Dimerumic Acid and Deferricoprogen Activate Ak Mouse Strain Thymoma/Heme Oxygenase-1 Pathways and Prevent Apoptotic Cell Death in 6-Hydroxydopamine-Induced SH-SY5Y Cells.

Abstract
Parkinson's disease (PD) is a neurodegenerative disorder, which can be modeled using the neurotoxin 6-hydroxydopamine (6-OHDA) to generate oxidative stress. Here, we studied the effects of the antioxidants deferricoprogen (DFC) and dimerumic acid (DMA), produced by rice fermented with Monascus purpureus NTU 568, on 6-OHDA-induced apoptosis in SH-SY5Y cells and their potential protective mechanisms. DMA and DFC inhibited 6-OHDA-induced apoptosis and cellular reactive oxygen species (ROS) in SH-SY5Y human neuroblastoma cells. Molecular analysis demonstrated associated upregulation of the Ak mouse strain thymoma (Akt), heme oxygenase-1 (HO-1), and signal-regulated kinase (ERK) pathways along with inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and p38 pathways and altered homodimeric glycoprotein, N-methyl-d-aspartate (NMDA) receptor, and immunoglobulin Fc receptor gene expression. These results suggested that the neuroprotection elicited by DMA and DFC against 6-OHDA-induced neurotoxicity was associated with the Akt, MAPK, and HO-1 pathways via regulating the gene expression of NMDA receptor, homodimeric glycoprotein, and immunoglobulin Fc receptor.
AuthorsWei-Ting Tseng, Ya-Wen Hsu, Tzu-Ming Pan
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 64 Issue 30 Pg. 5995-6002 (Aug 03 2016) ISSN: 1520-5118 [Electronic] United States
PMID27431098 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Diketopiperazines
  • Hydroxamic Acids
  • Reactive Oxygen Species
  • deferricoprogen
  • dimerumic acid
  • Oxidopamine
  • Heme Oxygenase-1
  • Proto-Oncogene Proteins c-akt
Topics
  • Antioxidants (therapeutic use)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cell Survival
  • Diketopiperazines (chemistry)
  • Heme Oxygenase-1 (metabolism)
  • Humans
  • Hydroxamic Acids (chemistry)
  • Oryza (chemistry)
  • Oxidative Stress
  • Oxidopamine (chemistry)
  • Parkinson Disease (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Reactive Oxygen Species (metabolism)

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