Norepinephrine transmitter metabolite is a selective cell death messenger in differentiated rat pheochromocytoma cells.
3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the monoamine oxidase A (MAO-A) metabolite of norepinephrine (NE) and epinephrine (Epi). Oxidative metabolites of amines are predicted toxins. In this study we determine the toxicity of DOPEGAL, its tautomer 2',3,4-trihydroxyacetophenone (THAP) as well as NE, Epi and their oxidative and methylated metabolites in cultures of differentiated PC-12 cells. At 59.5 microM DOPEGAL, THAP and Epi, but not NE or other NE or Epi metabolites decreased PC-12 cells by 43.8%, 26.7% and 16.8% respectively. DOPEGAL toxicity was concentration and time dependent. Possible implications for degenerative diseases are discussed.
Burke
W J
WJ
Department of Neurology, Saint Louis University Medical School, MO, USA.
Schmitt
C A
CA
Gillespie
K N
KN
Li
S W
SW
D000098:Acetophenones / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002396:Catechols; D002452:Cell Count; D016923:Cell Death; D002454:Cell Differentiation; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015290:Second Messenger Systems
C102214:2',3,4-trihydroxyacetophenone; D000098:Acetophenones; D000447:Aldehydes; D002396:Catechols; C007431:3,4-dihydroxyphenylglycolaldehyde; D008995:Monoamine Oxidase; D009638:Norepinephrine; D004837:Epinephrine