NOREPINEPHRINE TRANSMITTER METABOLITE GENERATES FREE-RADICALS AND ACTIVATES MITOCHONDRIAL PERMEABILITY TRANSITION - A MECHANISM FOR DOPEGAL-INDUCED APOPTOSIS

3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the monoamine oxidase A metabolite of norepinephrine (NE) and epinephrine. DOPEGAL, but neith er NE nor its other metabolites induces apoptosis in differentiated PC -12 cells by an unknown mechanism. To study the mechanism of DOPEGAL-i nduced apoptosis, we tested DOPEGAL and NE for their capacity to gener ate free radicals and to induce mitochondrial permeability transition (PT). Results show that DOPEGAL but not NE forms reactive free radical intermediates under oxidative stress and enhances Ca2+-mediated induc tion of the mitochondrial PT. Linkage of these events to apoptosis is described. Implications for degenerative diseases are discussed. (C) 1 998 Elsevier Science B.V.