Acrolein‐mediated mechanisms of neuronal death
- 17 April 2006
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 84 (1), 209-218
- https://doi.org/10.1002/jnr.20863
Abstract
It is well known that traumatic injury in the central nervous system can be viewed as a primary injury and a secondary injury. Increases in oxidative stress lead to breakdown of membrane lipids (lipid peroxidation) during secondary injury. Acrolein, an alpha,beta‐unsaturated aldehyde, together with other aldehydes, increases as a result of self‐propagating lipid peroxidation. Historically, most research on the pathology of secondary injury has focused on reactive oxygen species (ROS) rather than lipid peroxidation products. Little is known about the toxicology and cell death mediated by these aldehydes. In this study, we investigated and characterized certain features of cell death induced by acrolein on PC12 cells as well as cells from dorsal root ganglion (DRG) and sympathetic ganglion in vitro. In the companion paper, we evaluated a possible means to interfere with this toxicity by application of a compound that can bind to and inactivate acrolein. Here we use both light and atomic force microscopy to study cell morphology after exposure to acrolein. Administration of 100 μM acrolein caused a dramatic change in cell morphology as early as 4 hr. Cytoskeletal structures significantly deteriorated after exposure to 100 μM acrolein as demonstrated by fluorescence microscopy, whereas calpain activity increased significantly at this concentration. Cell viability assays indicated significant cell death with 100 μM acrolein by 4 hr. Caspase 3 activity and DNA fragmentation assays were performed and supported the notion that 100 μM acrolein induced PC12 cell death by the mechanism of necrosis, not apoptosis.Keywords
This publication has 19 references indexed in Scilit:
- Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord InjuryNeurochemical Research, 2005
- Pharmacological therapy of spinal cord injury during the acute phaseSpinal Cord, 2000
- A 1-Hour Enzyme-Linked Immunosorbent Assay for Quantitation of Acrolein- and Hydroxynonenal-Modified Proteins by Epitope-Bound Casein Matrix MethodAnalytical Biochemistry, 1999
- Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord InjuryJAMA, 1997
- Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up dataJournal of Neurosurgery, 1992
- Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydesFree Radical Biology & Medicine, 1991
- A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord InjuryThe New England Journal of Medicine, 1990
- Methylprednisolone and neurological function 1 year after spinal cord injuryJournal of Neurosurgery, 1985
- Glucocorticoids Potentiate Ischemic Injury to Neurons: Therapeutic ImplicationsScience, 1985
- Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injuryCanadian Journal of Physiology and Pharmacology, 1982