title: Short-term exposure of 4-hydroxynonenal induces mitochondria-mediated apoptosis in PC12 cells.
abstract: 4-Hydroxynonenal (4-HNE) is one of the most reactive aldehydic by-products of lipid peroxidation. The role of 4-HNE in the etiology of various neurodegenerative disorders including cerebral ischemia/reperfusion, Alzheimer's disease, Parkinson's disease, etc. has been documented. We and others have reported that long-term toxic insults of 4-HNE triggers apoptotic signals and oxidative stress in various cells. However, the status of apoptosis following short-term exposure and underlying mechanisms has not been explored so far. We studied the apoptotic changes in PC12 cells receiving short-term exposure of 4-HNE. A significant dose-dependent induction in reactive oxygen species (ROS) and early response markers (c-Fos, c-Jun, and GAP-43) were observed in cells exposed to 4-HNE (10, 25, and 50 µM) for 1h. Following the exposure of PC12 cells to 4-HNE, the levels of protein and messenger RNA expressions of P(53), Bax, and caspase 3 were significantly upregulated, whereas the levels of Bcl(2) was downregulated. We could record the apoptotic signals and ROS generation in PC12 cells receiving 4-HNE exposure for such a short period of time. Induction in the expression and activity of caspase 3 has also indicated the mitochondrial mediation in the apoptosis induction.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: M P
authors.initials: MP
authors.lastname: Kashyap
authors.forename: M
authors.initials: M
authors.lastname: Agarwal
authors.forename: A K
authors.initials: AK
authors.lastname: Singh
authors.forename: V K
authors.initials: VK
authors.lastname: Khanna
authors.forename: A A
authors.initials: AA
authors.lastname: Al-Khedhairy
authors.forename: J
authors.initials: J
authors.lastname: Musarrat
authors.forename: A B
authors.initials: AB
authors.lastname: Pant
authors.forename: S
authors.initials: S
authors.lastname: Jahan
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D019922:GAP-43 Protein; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053148:Caspase 3; C027576:4-hydroxy-2-nonenal