8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Neuronal death is an active, caspase-dependent process after moderate but not severe DNA damage.

      Journal of Neurochemistry
      Animals, Apoptosis, Caspases, metabolism, Cell Membrane, radiation effects, Cell Survival, Cells, Cultured, Chromosome Breakage, DNA, chemistry, DNA Damage, DNA Fragmentation, Dose-Response Relationship, Radiation, Fluorescent Dyes, Lipid Peroxidation, Neurons, cytology, Protein Synthesis Inhibitors, pharmacology, Rats, Rats, Sprague-Dawley, Time Factors, X-Rays

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults induce non apoptotic death, such as necrosis. The molecular targets that are damaged by these insults and ultimately induce cell death are not fully established. To determine if DNA damage can induce apoptotic or non apoptotic death depending on the severity, neurons were treated with up to 128 Gy of ionizing radiation. Such treatment induced a dose-related increase in DNA single-strand breaks but no immediate membrane disruption or lipid peroxidation. Following moderate doses of < or = 32 Gy, neuronal death had many characteristics of apoptosis including nuclear fragmentation and DNA laddering. Nuclear fragmentation and membrane breakdown after moderate DNA damage could be blocked by inhibition of active protein synthesis with cycloheximide and by inhibition of caspases. In contrast, cell death after doses of > 32 Gy was not blocked by cycloheximide or caspase inhibitors, and membrane breakdown occurred relatively early in the cell death process. These data suggest that cell death after high dose irradiation and severe DNA damage can occur by non apoptotic mechanisms and that blocking apoptotic pathways may not prevent death after severe damage.

          Related collections

          Author and article information

          Comments

          Comment on this article