PF9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] confers MAO-B independent neuroprotection in ER stress-induced cell death.
Endoplasmic reticulum (ER) stress has recently been proposed as one of the factors contributing to apoptotic cell death in Parkinson's disease (PD). Although MAO-B inhibitors have been suggested to exert neuroprotective effects in several experimental models of PD, their effectiveness against ER stress has not been fully determined. Therefore, we have studied the potential usefulness of PF9601N, a non-amphetamine-like MAO-B inhibitor, in preventing cell death in a cell culture model of ER stress. Exposure of human dopaminergic cell line SH-SY5Y to the ER stressor brefeldin A led to Golgi disassembly, activation of the unfolded protein response (UPR), and subsequent expression of the proapoptotic mediator GADD153/CHOP. In this context, PF9601N pretreatment prevented brefeldin A-induced UPR responses, thus blocking the expression of GADD153/CHOP and resulting apoptotic features. In summary, our data suggests that PF9601N is able to block the responses elicited by ER stress, thus preventing apoptotic cell death in brefeldin A-treated cells.
Sanz
Elisenda
E
Institut de Neurociències & Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. elisenda.sanz@uab.es
Quintana
Albert
A
Hidalgo
Juan
J
Marco
Jose Luis
JL
Unzeta
Mercedes
M
D000818:Animals; D020126:Brefeldin A / Q000378:metabolism; D053143:Caspase 2 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D013312:Stress, Physiological; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000378:metabolism
C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; C470996:N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D020126:Brefeldin A; D008995:Monoamine Oxidase; D053143:Caspase 2; D053453:Caspase 9