title: 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.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University , No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Tseng
authors.affiliation: SunWay Biotechnology Company , No. 139, Xing'ai Road, Taipei 11494, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University , No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.|SunWay Biotechnology Company , No. 139, Xing'ai Road, Taipei 11494, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D054659:Diketopiperazines / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D012275:Oryza / Q000737:chemistry; D018384:Oxidative Stress; D016627:Oxidopamine / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D054659:Diketopiperazines; D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; C576795:deferricoprogen; C552122:dimerumic acid; D016627:Oxidopamine; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt
keywords: Monascus purpureus-fermented rice; Parkinson’s disease; apoptosis; deferricoprogen; dimerumic acid