title: The reduction of R1, a novel repressor protein for monoamine oxidase A, in major depressive disorder.
abstract: The novel transcriptional repressor protein, R1 (JPO2/CDCA7L/RAM2), inhibits monoamine oxidase A (MAO A) gene expression and influences cell proliferation and survival. MAO A is implicated in several neuropsychiatric illnesses and highly elevated in major depressive disorder (MDD); however, whether R1 is involved in these disorders is unknown. This study evaluates the role of R1 in depressed subjects either untreated or treated with antidepressant drugs. R1 protein levels were determined in the postmortem prefrontal cortex of 18 untreated MDD subjects and 12 medicated MDD subjects compared with 18 matched psychiatrically normal control subjects. Western blot analysis showed that R1 was significantly decreased by 37.5% (p<0.005) in untreated MDD subjects. The R1 level in medicated MDD subjects was also significantly lower (by 30%; p<0.05) compared with control subjects, but was not significantly different compared with untreated MDD subjects. Interestingly, the reduction in R1 was significantly correlated with an increase (approximately 40%; p<0.05) in MAO A protein levels within the MDD groups compared with controls. Consistent with the change in MAO A protein expression, the MAO A catalytic activity was significantly greater in both MDD groups compared with controls. These results suggest that reduced R1 may lead to elevated MAO A levels in untreated and treated MDD subjects; moreover, the reduction of R1 has been implicated in apoptotic cell death and apoptosis has also been observed in the brains of MDD subjects. Therefore, modulation of R1 levels may provide a new therapeutic target in the development of more effective strategies to treat MDD.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Shakevia
authors.initials: S
authors.lastname: Johnson
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
authors.forename: Mark C
authors.initials: MC
authors.lastname: Austin
authors.forename: Paul R
authors.initials: PR
authors.lastname: Albert
authors.forename: Junming
authors.initials: J
authors.lastname: Wang
authors.forename: Warren L
authors.initials: WL
authors.lastname: May
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.forename: James C
authors.initials: JC
authors.lastname: Overholser
authors.forename: George
authors.initials: G
authors.lastname: Jurjus
authors.forename: Lesa
authors.initials: L
authors.lastname: Dieter
authors.forename: Chandra
authors.initials: C
authors.lastname: Johnson
authors.forename: Donald B
authors.initials: DB
authors.lastname: Sittman
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ou
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D003865:Major Depressive Disorder / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D012189:Retrospective Studies
chemical_list: C513450:CDCA7L protein, human; D012097:Repressor Proteins; D008995:Monoamine Oxidase