Cyclic nucleotides attenuate lipid peroxidation-mediated neuron toxicity.
Recent studies suggest that increased lipid peroxidation and lipid peroxidation products, such as 4-hydroxynonenal (HNE), contribute to neuronal loss in conditions associated with oxidative stress. The focus of the present study was to determine possible neuroprotective effects of elevated cyclic nucleotide levels against lipid peroxidation and HNE-mediated neural toxicity. Application of 8-bromo derivative analogs of cAMP or cGMP resulted in attenuation of HNE-induced increases in mitochondrial calcium, reactive oxygen species, and neuron loss. Similar results were obtained when neural cells were pretreated with the phosphodiesterase inhibitors zaprinast or isobutylmethylxanthanine (IBMX). These data are consistent with a possible neuroprotective role for elevated cyclic nucleotide levels in disorders associated with increases in lipid peroxidation and HNE.
Keller
J N
JN
Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Hanni
K B
KB
Mattson
M P
MP
Markesbery
W R
WR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D016716:PC12 Cells; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D009498:Neurotoxins; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D017382:Reactive Oxygen Species; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; C011145:zaprinast; D006152:Cyclic GMP; C027576:4-hydroxy-2-nonenal; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine