Calcium alters monoamine oxidase-A parameters in human cerebellar and rat glial C6 cell extracts: Possible influence by distinct signalling pathways

Abstract

Aims Calcium (Ca 2+) is known to augment monoamine oxidase-A (MAO-A) activity in cell cultures as well as in brain extracts from several species. This association between Ca 2+ and MAO-A could contribute to their respective roles in cytotoxicity. However, the effect of Ca 2+ on MAO-A function in human brain has as yet to be examined as does the contribution of specific signalling cascades. Main methods We examined the effects of Ca 2+ on MAO-A activity and on [ 3H]Ro 41-1049 binding to MAO-A in human cerebellar extracts, and compared this to its effects on MAO-A activity in glial C6 cells following the targeting of signalling pathways using specific chemical inhibitors. Key findings Ca 2+ enhances MAO-A activity as well as the association of [ 3H]Ro 41-1049 to MAO-A in human cerebellar extracts. The screening of neuronal and glial cell cultures reveals that MAO-A activity does not always correlate with the expression of either mao-A mRNA or MAO-A protein. Inhibition of the individual PI3K/Akt, ERK and p38(MAPK) signalling pathways in glial C6 cells all augment basal MAO-A activity. Inhibition of the p38(MAPK) pathway also augments Ca 2+-sensitive MAO-A activity. We also observe the inverse relation between p38(MAPK) activation and MAO-A function in C6 cultures grown to full confluence. Significance The Ca 2+-sensitive component to MAO-A activity is present in human brain and in vitro studies link it to the p38(MAPK) pathway. This means of influencing MAO-A function could explain its role in pathologies as diverse as neurodegeneration and cancers.