Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.
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PMID:Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa. 1107 Mar 31

Fibromyalgia is a form of non-articular rheumatism characterised by long term (>3 months) and widespread musculoskeletal aching, stiffness and pressure hyperalgesia at characteristic soft tissue sites, called soft tissue tender points. The biophysiology of fibromyalgia, however, has remained elusive and the treatment remains mainly empirical. This article reviews the neuroendocrine-immune pathophysiology of fibromyalgia. There is no major evidence that fibromyalgia is accompanied by activation of the inflammatory response system, by immune activation or by an inflammatory process. There is some evidence that fibromyalgia is accompanied by some signs of immunosuppression, suggesting that immunomodifying drugs could have potential in the treatment of fibromyalgia. Recent trials with cytokines, such as interferon-alpha, have been undertaken in patients with fibromyalgia. Immunotherapy with these agents, however, may induce symptoms reminiscent of fibromyalgia and depression in a considerable number of patients. Lowered serum activity of prolyl endopeptidase (PEP), a cytosolic endopeptidase that cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass, may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides, e.g. substance P. Trials with PEP agonists could be worthwhile in fibromyalgia. The muscle energy depletion hypothesis of fibromyalgia is supported by findings that this condition is accompanied by lowered plasma levels of branched chain amino acids (BCAAs), i.e. valine, leucine and isoleucine. Since there is evidence that BCAA supplementation decreases muscle catabolism and has ergogenic values, a supplemental trial with BCAAs in fibromyalgia appears to be justified.
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PMID:Neuroendocrine and immune aspects of fibromyalgia. 1154 93

Immunotherapy with interferon-alpha (IFN-alpha) induces neuropsychiatric side effects, most notably depression. In hepatitis patients treated with IFN-alpha, severity of depression correlates with a decrease in serum activity of dipeptidyl peptidase IV (DPP-IV, EC 3.4.14.5), a membrane-bound protease involved in the cleavage of cytokines and neuroactive peptides. Abnormal serum activity of the cytosolic peptidase prolyl endopeptidase (PEP, EC 3.4.21.26, postprolyl cleaving enzyme, prolyl oligopeptidase) has been documented in patients with a variety of psychiatric disorders, most consistently in mood disorders. The serum activity of PEP and DPP-IV was measured before and after 4 weeks of high-dose induction treatment with IFN-alpha in 18 patients with high-risk melanoma. In this exploratory study, we show a clear decrease in the serum activity of PEP after 4 weeks of treatment with IFN-alpha. This decrease was not related to changes in hematologic parameters. In contrast, serum activity of DPP-IV did not change. Further studies focusing on a possible role of PEP in the pathophysiology of IFN-alpha-induced depression are warranted.
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PMID:Serum activity of prolyl endopeptidase, but not of dipeptidyl peptidase IV, is decreased by immunotherapy with IFN-alpha in high-risk melanoma patients. 1529 52

Abnormal activity in peripheral blood of the cytosolic enzyme prolyl endopeptidase (PEP, EC 3.4.21.26, post prolyl cleaving enzyme, prolyl oligopeptidase) has been found in patients with a variety of psychiatric disorders, most consistently in mood disorders. Mood disturbance is a well-known side effect of immunotherapy with interferon-alpha (IFN-alpha). Earlier, we documented a decrease in serum PEP activity in the first 4 weeks of treatment with IFN-alpha. In 24 patients (16 men, 8 women, median age 60.5 years, range 47-72 years) with metastatic renal cell carcinoma (RCC), psychiatric assessment and blood sampling were performed before and at 4 and 8 weeks and at 6 months after initiation of treatment with IFN-alpha. No episodes of depression were observed, and the sum score and the scores on the subscales for depression and hostility of the Symptom Check List-90 (SCL-90) did not change during follow-up, whereas the anxiety scores were somewhat lower at 4 and 8 weeks compared with baseline. No change in plasma PEP activity and no relationships between change in psychiatric parameters and change in plasma PEP activity were found. As more subtle relationships between PEP activity and psychiatric status could have easily been obscured, a role for PEP in the pathophysiology of IFN-alpha-induced mood disturbance can neither be confirmed nor excluded.
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PMID:Plasma activity of prolyl endopeptidase in relation to psychopathology during immunotherapy with IFN-alpha in patients with renal cell carcinoma. 1854 58

Prolyl oligopeptidase or prolyl endopeptidase (PREP; EC 3.4.21.26) is an atypical serine protease that hydrolyses peptides and peptide hormones after proline in peptides up to around 30 residues long. Evidence suggests an involvement in learning and memory, and the enzyme is implicated in diseases including amnesia and depression. The first crystal structures determined, of the porcine enzyme, provided direct insight into the mechanisms of substrate size selectivity, substrate specificity, and catalysis. However in these structural studies the enzyme is in a closed state, even in the absence of ligand, leaving questions as to how substrates and products can enter and exit the enclosed central cavity that houses the active site. More recent crystal structures of bacterial PREP have captured the enzyme in an open state, revealing the true extent and nature of the structural dynamics involved, and illuminating an induced fit mode of catalysis and regulation. Molecular modeling has further contributed to our understanding of the conformational changes that occur during catalysis. Here we review the data that has led to our current understanding of the structure and dynamics of this biologically and pharmaceutically important enzyme.
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PMID:Prolyl oligopeptidase structure and dynamics. 2122 26

We studied the dynamics of activity of dipeptidyl peptidase IV (DP-IV) and prolyl endopeptidase (PEP) in the frontal cortex, hypothalamus, striatum, nucleus accumbens, and hippocampus of rats with experimental anxiety-depression state induced by administration of methionyl-2(s)-cyano-pyrrolidine, an inhibitor of DPP-IV, in the early postnatal period. In 1-month-old experimental males, PEP and DP-IV activities increased in the frontal cortex and hypothalamus, while in 1-month-old experimental females PEP activity increased in the hippocampus and DP-IV activity increased in all studied brain structures. At the age of 3 months, increased PEP activity in the hypothalamus and nucleus accumbens was detected in males and decreased DP-IV activity in the nucleus accumbens and decreased PEP activity in the hippocampus were detected in females. At the age of 7 months, PEP activity increased in the frontal cortex and striatum and DP-IV activity increased in all studied brain structures in males; in 7-months-old females, activity of both enzymes increased in the striatum.
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PMID:Activities of proline-specific peptidases in brain structures of rats with experimental anxiety-depressive state caused by administration of dipeptidyl peptidase IV inhibitor in the early postnatal period. 2248 5

Activities of prolyl endopeptidase and dipeptidyl peptidase IV in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus were measured in rats with the experimental anxious-depressive syndrome induced by treatment with a dipeptidyl peptidase IV inhibitor during the early postnatal period (days 5-18). Prolyl endopeptidase activity was elevated in the frontal cortex, hypothalamus, and nucleus accumbens. Increased activity of dipeptidyl peptidase IV was observed in the hypothalamus and striatum. Norepinephrine/serotonin reuptake inhibitor, imipramine, and noncompetitive prolyl endopeptidase inhibitor, benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, were shown to abolish depression-like behavior of animals in the forced swimming test. These compounds had a normalizing effect on activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats.
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PMID:Effect of imipramine and prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on activity of proline-specific peptidases in the brain of rats with experimental anxious-depressive syndrome. 2280 98

High activities of prolyl endopeptidase and dipeptidylpeptidase IV in the striatum and of prolyl endopeptidase in the frontal cortex were recorded in rats with stress-induced depression-like state (behavioral despair) developed in the Porsolt forced swimming test. Acute injection of benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine (prolyl endopeptidase noncompetitive synthetic inhibitor) in a dose of 1 mg/kg prevented the development of behavioral despair and the increase of prolyl endopeptidase and dipeptidylpeptidase IV activities in the brain structures. In a dose of 2 mg/kg prolyl endopeptidase inhibitor did not modify the development of behavioral despair, but prevented the increase of prolyl endopeptidase and dipeptidylpeptidase IV activities in the striatum.
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PMID:Benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, a prolyl endopeptidase inhibitor, modulates depression-like behavior of rats in forced swimming test and activities of proline-specific peptidases in the brain structures. 2365 79

The effects of noncompetitive prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine were studied in rats with the experimental dopamine deficiency-dependent depressive syndrome induced by systemic injections of a pre-neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin for 14 days. The inhibitor (3.0 mg/kg, i.p., 30 min before pre-neurotoxin injection on days 8-14) alleviated depression symptoms and promoted normalization of behavioral activity after drug withdrawal. The obtained data reflected therapeutic antidepressant properties of inhibitor for prolyl endopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine.
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PMID:Effect of prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on the course of experimental depressive syndrome in rats. 2413 Sep 86

In two models of depression-like state--"behavioral despair" and experimental dopamine deficit-dependent MPTP-induced depression-like syndrome--as well as in a model of anxiety-depression-like state induced by dipeptidyl peptidase IV inhibitor methionyl-2(s)-cyanopyrrolidine administered in early postnatal period, the symptoms of behavioral depression in rats in the forced swim test were accompanied by the increase of corticosterone level in blood serum. In every model non-competitive prolyl endopeptidase (PEP) inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine showed antidepressant-like properties preventing the development of depressive-like behavior. PEP Inhibitor also prevented the increase of serum corticosterone level in the models of "behavioral despair" and anxiety-depressive state, but not in the model of MPTP-induced depression-like syndrome. These findings testify for the involvement of hypothalamic-pituitary-adrenal system in the implementation of depression-like behavior in the specified models of depression-like state.
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PMID:[Blood serum corticosterone level in modeling depression-like states in rats]. 2464 Jul 66


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