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 neither NE nor its other metabolites induces apoptosis in differentiated PC-12 cells by an unknown mechanism. To study the mechanism of DOPEGAL-induced apoptosis, we tested DOPEGAL and NE for their capacity to generate 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 Ca 2+-mediated induction of the mitochondrial PT. Linkage of these events to apoptosis is described. Implications for degenerative diseases are discussed.