Neuroprotective action of genipin on tunicamycin-induced cytotoxicity in neuro2a cells.
Accumulation of unfolding or misfolded proteins within the lumen of the endoplasmic reticulum (ER) triggers ER stress, and sustained ER stress ultimately leads to cell death. Both of these events are involved in the activation of glucose-regulated protein of 78 kDa (GRP78, also known as Bip), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP, also known as growth arrest and DNA damage-inducible gene 153 (GADD153)), and caspase-12. ER stress has been shown to be involved in neurodegenerative disorders, such as Alzheimer, Parkinson, and polyglutamine diseases. We previously showed that genipin, a natural iridoid compound, has a protective effect against amyloid-beta (Abeta)-induced cytotoxicity. Here, we studied the protective effects of genipin on cytotoxicity induced in Neuro2a cells by the specific ER stress inducer tunicamycin (TM). TM treatment significantly reduced cell viability in a dose-dependent manner. Genipin dramatically rescued the cells against TM-induced cell death. In addition, genipin suppressed ER stress-induced upregulation of CHOP and GRP78. These data suggest that genipin is effective at protecting against neurodegenerative disorders.
Tanaka
Masayuki
M
Organization for Frontier Research in Preventive Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hokuriku University. mtanaka@inst-hsc.jp
Yamazaki
Matsumi
M
Chiba
Kenzo
K
D000818:Animals; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D057889:Iridoid Glycosides; D039823:Iridoids / Q000494:pharmacology*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017510:Protein Folding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000633:toxicity*
D022762:CCAAT-Enhancer-Binding Proteins; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D057889:Iridoid Glycosides; D039823:Iridoids; D018696:Neuroprotective Agents; D014415:Tunicamycin; D051742:Transcription Factor CHOP; C007834:genipin; C506440:Casp12 protein, mouse; D053454:Caspase 12