Decreased tyrosine transport in fibroblasts from schizophrenics: Implications for membrane pathology

Ramchand, C.N.; Peet, Malcolm; Clark, A.E.; Gliddon, A.; Hemmings, G.P.

doi:10.1016/s0952-3278(96)90146-5

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…These findings in combination with other studies indicate dysfunctional signal transduction as well as altered membrane metabolism and composition, considering that amino acid transporters are embedded in cell membranes [21,22]. BD has been previously related to membrane dysregulation through the membrane theory.…”

Section: Aberrant Amino Acid Transport and Membrane Dysfunctionssupporting

confidence: 78%

Gene Expression Analysis of Fibroblasts from Patients with Bipolar Disorder

Logotheti¹,

Papadodima²

2016

J Neuropsychopharmacol Mental Health

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Bipolar disorder is a severe, lifelong psychiatric disease. The main underlying pathophysiology of the disease is still incomprehensible. Various studies have suggested that many genes of small impact in combination with environmental factors contribute to the expression of the disease. In this study comparative transcriptomic profiling to characterize skin fibroblasts' gene expression of bipolar disorder patients compared to healthy controls has been performed. Skin fibroblast cells from bipolar disorder patients (n=10) and marched healthy controls (n=5) have been cultured. RNA was extracted and then hybridized onto Illumina Human HT-12 v4 Expression BeadChips. Differentially expressed genes between bipolar disorder samples and healthy controls were identified by performing unequal t-test on log 2 transformed expression values. The resulting gene list was obtained by setting the p-value threshold to 0.05 and by removing genes that presented a fold change ≥ |0.5| (in log 2 scale). We concluded to 457 differentially expressed genes. Among them 127 showed an upregulation and 330 were downregulated. Τhe expression alterations of selected genes were validated by quantitative real-time polymerase chain reaction. In order to derive better insight into the biological mechanisms related to the differentially expressed genes, the lists of significant genes were subjected to pathway analysis and target prioritization indicating various processes such as calcium ion homeostasis, positive regulation of apoptotic process and cellular response to retinoic acid.

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Section: Aberrant Amino Acid Transport and Membrane Dysfunctionssupporting

confidence: 78%

Gene Expression Analysis of Fibroblasts from Patients with Bipolar Disorder

Logotheti¹,

Papadodima²

2016

J Neuropsychopharmacol Mental Health

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“…When using the fibroblast cell model, previous findings by our group [23-29] and others [30] have shown a disturbed membrane transport of tyrosine in a number of psychiatric disorders, such as schizophrenia, autism and bipolar disorder, Moreover, in a previous study by our group, we found that children with autism had an increased transport capacity of alanine across cell membranes [24]. An elevated transport of alanine across the BBB might influence the transport of other amino acids that are of vital importance for normal brain activity, since amino acids using the same transporter compete for transport [13,15].…”

Section: Introductionmentioning

confidence: 99%

Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study

et al. 2011

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BackgroundThe catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport.MethodsFibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (Vmax) and affinity constant (Km) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test.ResultsThe ADHD group had significantly decreased Vmax (p = 0.039) and Km (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher Vmaxof alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group.ConclusionsTryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.

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“…The dynamics and the mobility of membrane proteins are under the control of the fluidity of the lipid bilayer, which may be influenced by the membrane‐lipid pattern, including both the composition and the arrangements of lipids in the plasma membrane. A perturbation in the membrane‐lipid fluidity may produce an altered interaction of membrane proteins with their specific ligands and affect membrane permeability accordingly [26,27]. This is the first study demonstrating strongly decreased l ‐arginine uptake in platelets from type‐2 diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Impaired l‐arginine uptake in platelets from type‐2 diabetic patients

Signorello

Giovine

Pascale

et al. 2001

Biotech and App Biochem

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The L-arginine uptake of resting platelets from type-2 diabetic patients and control subjects was measured and the kinetic parameters defined. The effect of platelet stimulation with agonists was also investigated. Kinetic studies showed that the K(m) value for L-arginine transport was not different in patients compared with control subjects, while V(max) was significantly decreased in patients compared with controls. Moreover, agonists able to mobilize Ca(2+) produced a further decrease in the L-arginine uptake in controls and in patients, suggesting that Ca(2+) intracellular levels down-regulate L-arginine transport in platelets from both control subjects and patients. Data suggest that drugs designed to control intracellular Ca(2+) might restore platelet function in diabetic patients.

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Decreased tyrosine transport in fibroblasts from schizophrenics: Implications for membrane pathology

Cited by 20 publications

References 34 publications

Gene Expression Analysis of Fibroblasts from Patients with Bipolar Disorder

Gene Expression Analysis of Fibroblasts from Patients with Bipolar Disorder

Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study

Impaired l‐arginine uptake in platelets from type‐2 diabetic patients

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