None of the authors has any commercial associations that might pose a conflict of interest in connection with this manuscript.
Interaction of calbindin D28k and inositol monophosphatase in human postmortem cortex: possible implications for bipolar disorder
Version of Record online: 14 JAN 2005
Volume 7, Issue 1, pages 42–48, February 2005
How to Cite
Shamir, A., Elhadad (Rosolio), N., Belmaker, R. H. and Agam, G. (2005), Interaction of calbindin D28k and inositol monophosphatase in human postmortem cortex: possible implications for bipolar disorder. Bipolar Disorders, 7: 42–48. doi: 10.1111/j.1399-5618.2004.00162.x
- Issue online: 14 JAN 2005
- Version of Record online: 14 JAN 2005
- Received 25 November 2003, revised and accepted for publication 30 July 2004
- bipolar disorder;
- calbindin D28k;
- inositol monophosphatase;
- postmortem brain;
- protein levels
Objectives: Therapeutically relevant concentrations of lithium (Li) exert an uncompetitive inhibition on inositol monophosphatase (IMPase). It has recently been shown that calbindin D28k (calbindin) activates IMPase. Purified calbindin attaches to a specific amino acid sequence on purified IMPase enhancing its activity by several hundred fold. We studied whether calbindin activates IMPase in postmortem human brain crude homogenate, whether differences in calbindin levels between lymphocytes and brain may be responsible for our previous finding of reduced IMPase activity in lymphocytes but not brain of bipolar patients, and whether calbindin protein levels are altered in postmortem brain from bipolar patients versus control subjects and schizophrenic and major depressive patients.
Methods: IMPase activity in human postmortem brain specimens with or without 10 μM human recombinant calbindin was quantified spectrophotometrically in an enzyme-linked immunosorbent assay (ELISA) reader. Calbindin protein levels in postmortem brain were determined using Western blot analysis.
Results: Supplementation of human recombinant calbindin to postmortem human brain crude homogenate enhanced IMPase activity by 3.5-fold. No difference in postmortem temporal cortex calbindin protein levels was found between bipolar patients versus comparison groups. Two-fold higher calbindin protein levels were found in Li-treated bipolar patients compared with other bipolar patients. Subchronic Li treatment in mice did not affect brain calbindin protein levels significantly. Chronic Li treatment reduced calbindin protein levels in the frontal cortex but not in the hippocampus.
Conclusions: Calbindin is a physiological activator of IMPase in human brain. Protein levels of calbindin are not altered in postmortem temporal cortex of bipolar patients.