Disease relevance of C05665

• Considered together, these results indicate that polyamine oxidase-derived 3-aminopropanal is a mediator of the brain damaging sequelae of cerebral ischemia, which can be therapeutically modulated [1].
• We now report that 3-aminopropanal accumulates in the ischemic brain within 2 h after permanent forebrain ischemia in rats [1].
• Here we report that increased levels of 3-aminopropanal-modified protein levels in humans after aneurysmal subarachnoid hemorrhage correlate with the degree of cerebral injury as measured by admission Hunt/Hess grade [2].
• In our studies of acrolein and 3-aminopropanal toxicity, using an immortalized retinal cell line, we found that aldehyde sequestration with phenelzine was neuroprotective [3].

High impact information on C05665

• Cerebral ischemia enhances polyamine oxidation: identification of enzymatically formed 3-aminopropanal as an endogenous mediator of neuronal and glial cell death [1].
• Glial cell cultures exposed to 3-aminopropanal undergo apoptosis (LD50 = 160 microM), whereas neurons are killed by necrotic mechanisms (LD50 = 90 microM) [1].
• The tetrapeptide caspase 1 inhibitor (Ac-YVAD-CMK) prevents 3-aminopropanal-mediated apoptosis in glial cells [1].
• Cerebral ischemia stimulates increased activity of polyamine oxidase, a ubiquitous enzyme that catabolizes polyamines to produce 3-aminopropanal [2].
• The recombinant enzyme shows an optimal pH value of 8.0 and is able to oxidize rapidly spermine to spermidine and 3-aminopropanal and fails to act upon spermidine and N(1)-acetylpolyamines [4].

Anatomical context of C05665

• Cytotoxic levels of 3-aminopropanal are achieved before the onset of significant cerebral cell damage, and increase in a time-dependent manner with spreading neuronal and glial cell death [1].
• Administration of N-2-MPG in clinically relevant doses to rats significantly reduces cerebral 3-aminopropanal-modified protein immunoreactivity and infarct volume in a standardized model of middle cerebral artery occlusion, even when the agent is administered after the onset of ischemia [2].

Associations of C05665 with other chemical compounds

• While deletion of the nuclear gene encoding the unrelated mitochondrial Ald5p resulted in an enhanced requirement for pantothenic acid pathway metabolites, we found no evidence to indicate that the Ald5p functions directly in the conversion of 3-aminopropanal to beta-alanine [5].
• To this end, we evaluated hydroxylamines as aldehyde-trapping agents in an in vitro model of neurodegeneration induced by the reactive aldehyde, 3-aminopropanal (3-AP), a product of polyamine oxidase metabolism of spermine and spermidine [6].
• The flavoprotein SMO is the most recently characterized catabolic enzyme, preferentially oxidizing SPM to SPD, 3-aminopropanal and H(2)O(2) [7].

Gene context of C05665

• As the product of DAP oxidation, 3-amino-propanal (APAL) was detected by mass spectrometry and confirmed to be a potent noncompetitive inhibitor of GPAO [8].
• In this investigation the bovine serum amine oxidase catalyzed oxidation of polyamines has been studied by HPLC analysis of dansylated reaction products with or without NaBH4 reduction and by NMR spectroscopy of the reaction products and 3-aminopropanal was found to be a major reaction product [9].

References