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


METHODS
We examined the effects of Ca(2+) on MAO-A activity and on [(3)H]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.


RESULTS
Ca(2+) enhances MAO-A activity as well as the association of [(3)H]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.


CONCLUSIONS
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.
Cao
Xia
X
Cell Signalling Laboratory, Department of Psychiatry, B45 HSB, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada.
Li
Xin-Min
XM
Mousseau
Darrell D
DD
D000368:Aged; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005909:Glioblastoma; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013844:Thiazoles / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D013844:Thiazoles; C063456:Ro 41-1049; D008995:Monoamine Oxidase; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium