BACKGROUND: Inhibition of prolyl oligopeptidase (PO) in primary neuronal cultures has been shown to reverse the effect of the common mood-stabilizers lithium, valproic acid and carbamazepine. In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia. However, this association is complicated by the discovery in bovine plasma of a Z-Pro-prolinal-insensitive peptidase (ZIP), a novel enzyme that cleaves the same substrate as PO. METHODS: We developed an assay to distinguish between ZIP and PO and measured both activities in plasma from 48 BD and 50 schizophrenic patients undergoing treatment and compared them with 50 control subjects. RESULTS: ZIP activity is restricted to blood plasma, whereas PO activity is present in the cytosol of lymphocytes, but can also be detected in blood plasma. Significant decreases in their plasma activities were found between treated BD (p = 0.007 and 0.03 respectively) but not schizophrenic (p > 0.05) patients and controls. CONCLUSIONS: We have found that the enzyme activity previously reported as plasma PO actually comprises two enzymes, PO and ZIP. This study shows a statistically significant decrease of both enzymes in BD patients undergoing lithium treatment. No statistically significant change in PO or ZIP activity is observed in schizophrenic patients.
BACKGROUND: Inhibition of prolyl oligopeptidase (PO) in primary neuronal cultures has been shown to reverse the effect of the common mood-stabilizers lithium, valproic acid and carbamazepine. In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia. However, this association is complicated by the discovery in bovine plasma of a Z-Pro-prolinal-insensitive peptidase (ZIP), a novel enzyme that cleaves the same substrate as PO. METHODS: We developed an assay to distinguish between ZIP and PO and measured both activities in plasma from 48 BD and 50 schizophrenicpatients undergoing treatment and compared them with 50 control subjects. RESULTS:ZIP activity is restricted to blood plasma, whereas PO activity is present in the cytosol of lymphocytes, but can also be detected in blood plasma. Significant decreases in their plasma activities were found between treated BD (p = 0.007 and 0.03 respectively) but not schizophrenic (p > 0.05) patients and controls. CONCLUSIONS: We have found that the enzyme activity previously reported as plasma PO actually comprises two enzymes, PO and ZIP. This study shows a statistically significant decrease of both enzymes in BD patients undergoing lithium treatment. No statistically significant change in PO or ZIP activity is observed in schizophrenicpatients.
Authors: B J Eickholt; G J Towers; W J Ryves; D Eikel; K Adley; L M J Ylinen; N H Chadborn; A J Harwood; H Nau; R S B Williams Journal: Mol Pharmacol Date: 2005-02-01 Impact factor: 4.436
Authors: Jason King; Melanie Keim; Regina Teo; Karin E Weening; Mridu Kapur; Karina McQuillan; Jonathan Ryves; Ben Rogers; Emma Dalton; Robin S B Williams; Adrian J Harwood Journal: PLoS One Date: 2010-06-17 Impact factor: 3.240