Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal Academic Article uri icon

Overview

MeSH Major

  • Aldehydes
  • Brain Ischemia
  • Glycine
  • Propylamines

abstract

  • Cerebral ischemia stimulates increased activity of polyamine oxidase, a ubiquitous enzyme that catabolizes polyamines to produce 3-aminopropanal. 3-Aminopropanal is a reactive aldehyde that mediates progressive neuronal necrosis and glial apoptosis. 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. In vitro screening of clinically approved drugs reveals that N-2-mercaptopropionyl glycine (N-2-MPG), an agent clinically approved for prevention of renal stones in patients with cysteinuria, significantly inhibits the cytotoxicity of 3-aminopropanal. N-2-MPG reacts with 3-aminopropanal to yield a nontoxic thioacetal adduct, as confirmed by electrospray ionization mass spectroscopy. 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. These results implicate 3-aminopropanal as a therapeutic target for cerebral ischemia.

publication date

  • April 16, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC122812

Digital Object Identifier (DOI)

  • 10.1073/pnas.082609299

PubMed ID

  • 11943872

Additional Document Info

start page

  • 5579

end page

  • 84

volume

  • 99

number

  • 8