Acrolein-induced cell death in PC12 cells: role of mitochondria-mediated oxidative stress.
Oxidative stress has been implicated in acrolein cytotoxicity in various cell types, including mammalian spinal cord tissue. In this study we report that acrolein also decreases PC12 cell viability in a reactive oxygen species (ROS)-dependent manner. Specifically, acrolein-induced cell death, mainly necrosis, is accompanied by the accumulation of cellular ROS. Elevating ROS scavengers can alleviate acrolein-induced cell death. Furthermore, we show that exposure to acrolein leads to mitochondrial dysfunction, denoted by the loss of mitochondrial transmembrane potential, reduction of cellular oxygen consumption, and decrease of ATP level. This raises the possibility that the cellular accumulation of ROS could result from the increased production of ROS in the mitochondria of PC12 cells as a result of exposure to acrolein. The acrolein-induced significant decrease of ATP production in mitochondria may also explain why necrosis, not apoptosis, is the dominant type of cell death. In conclusion, our data suggest that one possible mechanism of acrolein-induced cell death could be through mitochondria as its initial target. The subsequent increase of ROS then inflicts cell death and further worsens mitochondria function. Such mechanism may play an important role in CNS trauma and neurodegenerative diseases.
Luo
Jian
J
Center for Paralysis Research, Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Robinson
J Paul
JP
Shi
Riyi
R
D000171:Acrolein / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles
D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D000171:Acrolein; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C022616:thiazolyl blue