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- Venizelos, Nikolaos, 1946-, et al.
(författare)
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Availability Of Tyrosine And Tryptophan, Precursors Of Dopamine And Serotonin And Neuropsychiatric Disorders : A Review
- 2015
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Ingår i: Pluralism in psychiatry. - Bologna, Italy : Medimond. - 9788875877224 ; , s. 49-54
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Bokkapitel (refereegranskat)abstract
- The large neutral amino acids tyrosine and tryptophan are precursors of the neurotransmitters dopamine and serotonin and their availability in the brain may influence neurotransmission. Disturbed neurotransmitter systems, such as the dopaminergic, noradrenergic and serotoninergic systems are implicated in the pathogenesis of neuropsychiatric disorders, including schizophrenia, bipolar disorder, autism and attention deficit hyperactivity disorder (ADHD).The primary aim of this study is to outline the findings/evidence from different investigations in vitro, concerning aberrant amino acid (tyrosine, tryptophan and alanine) transport in fibroblasts obtained from patients with schizophrenia and their relatives, bipolar-I disorder, autism and ADHD disorders.The outlines of the findings presented in this study provide evidence that amino acids, tyrosine and tryptophan are strongly involved in schizophrenia, bipolar disorder, autism and ADHD.
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| 2. |
- Ahmad, Abrar, 1984-, et al.
(författare)
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Prognostic Effect of Vascular Endothelial Growth Factor +936C/T Polymorphism on Tumor Growth Pattern and Survival in Patients Diagnosed with Colon Carcinoma
- 2016
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Ingår i: Journal of Tumor Research. - : OMICS International. - 2684-1258. ; 2:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Vascular endothelial growth factor (VEGF) is considered as endothelial cell-specific mitogen that plays an important role in the process of angiogenesis, thereby affecting the prognosis of tumor as angiogenesis is a crucial phase in tumor growth and metastasis. Accordingly, we carried out a case-control study to assess whether VEGF rs3025039 polymorphism affects the growth pattern and susceptibility to colon carcinoma.Materials and methods: One hundred and fifty, formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with colon carcinoma and the same number of blood controls were used in the present study. VEGF +936 C>T (rs3025039) polymorphism was evaluated by pyrosequencing. Computer image analysis was used to analyse the growth pattern of the colon carcinoma tumor by using cytokeratin-8 stained slides.Results: A heterozygous genotype TC in rs3025039 polymorphism was found as a significantly protective genotype as compared to homozygous genotypes (CC and TT). However we found no significant correlation between investigated polymorphisms, tumor growth pattern, 5 years survival and other clinicopathological parameters.Conclusion: We concluded that the heterogenous genotype of VEGF rs3025039 polymorphism appears to be a protective factor for colon carcinoma that could be a useful marker in follow-up studies and may be a genetic determinant for colon carcinoma.
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| 3. |
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| 4. |
- Bjerkenstedt, Lars, et al.
(författare)
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Support for limited brain availability of tyrosine in patients with schizophrenia
- 2006
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Ingår i: International Journal of Neuropsychopharmacology. - 1461-1457 .- 1469-5111. ; 9, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- Several mechanisms have been suggested to account for altered dopaminergic neurotransmission in schizophrenia. The brain is the only organ for which amino-acid transport is limited and competition for transport over the blood-brain barrier (BBB) occurs at physiological plasma concentrations. One line of research suggests that patients with schizophrenia have altered brain levels of the essential amino acid tyrosine, the precursor for the synthesis of dopamine. The most common hypothesis is that less tyrosine is available because of competition with elevated levels of other amino acids. By consequence, the synthesis of dopamine in the brain will decrease. In contrast, another line of evidence suggests a change in the affinity for one of the transport proteins. A limitation of this research has been that the systems for amino-acid transport across the BBB have not been fully characterized at a molecular or functional level. The L system is the major system for transport of tyrosine across cell membranes including the BBB. The A system is also involved in this transport. Earlier in-vitro studies using fibroblasts have demonstrated a normal L system in schizophrenia but nevertheless reduced tyrosine transport. The combination of molecular research, fibroblast techniques, and brain imaging provides a new basis for clinical research on the role of amino-acid membrane transport in schizophrenia.
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| 5. |
- Comasco, Erika, 1982-, et al.
(författare)
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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
- 2017
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Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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| 6. |
- Engwall, Magnus, 1965-, et al.
(författare)
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Polycyclic aromatic hydrocarbons (PAHs) reduce hepatic beta-oxidation of fatty acids in chick embryos
- 2013
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 20:3, s. 1881-1888
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons (PAHs) are widespread fused-ring contaminants formed during incomplete combustion of almost all kind of organic materials from both natural and anthropogenic sources. Some PAHs have been shown to be carcinogenic to humans, and a wide range of PAHs are found in wildlife all around the globe including avian species. The purpose of this project was to assess the effects of a standard mixture of 16 PAHs (United States Environmental Protection Agency) on the hepatic fatty acid beta-oxidation in chicken embryos (Gallus gallus domesticus) exposed in ovo. The hepatic beta-oxidation was measured using a tritium release assay with [9,10-H-3]-palmitic acid (16:0) as substrate. Treated groups were divided into groups of 0.05, 0.1, 0.3, 0.5, and 0.8 mg PAHs/kg egg weight. The hepatic beta-oxidation was reduced after exposure in ovo to the 16 PAHs mixture compared to control. The mechanisms causing reduced fatty acid oxidation in the present study are unclear, however may be due to deficient membrane structure, the functionality of enzymes controlling the rate of fatty acid entering into the mitochondria, or complex pathways connected to endocrine disruption. To the best of our knowledge, this is the first time a PAH-caused reduction of hepatic beta-oxidation of fatty acids in avian embryos has been observed. The implication of this finding on risk assessment of PAH exposure in avian wildlife remains to be determined.
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| 7. |
- Fernell, Elisabeth, et al.
(författare)
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Aberrant amino acid transport in fibroblasts from children with autism
- 2007
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Ingår i: Neuroscience Letters. - Amsterdam : Elsevier. - 0304-3940 .- 1872-7972. ; 418:1, s. 82-86
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Tidskriftsartikel (refereegranskat)abstract
- Autism is a developmental, cognitive disorder clinically characterized by impaired social interaction, communication and restricted behaviours. The present study was designed to explore whether an abnormality in transport of tyrosine and/or alanine is present in children with autism. Skin biopsies were obtained from 11 children with autism (9 boys and 2 girls) fulfilling the DSM-IV diagnostic criteria for autistic disorder and 11 healthy male control children. Transport of amino acids tyrosine and alanine across the cell membrane of cultured fibroblasts was studied by the cluster tray method. The maximal transport capacity, Vmax and the affinity constant of the amino acid binding sites, Km, were determined. Significantly increased Vmax for alanine (p = 0.014) and increased Km for tyrosine (p = 0.007) were found in children with autism. The increased transport capacity of alanine across the cell membrane and decreased affinity for transport sites of tyrosine indicates the involvement of two major amino acid transport systems (L- and A-system) in children with autism. This may influence the transport of several other amino acids across the blood–brain-barrier. The significance of the findings has to be further explored. © 2007 Elsevier Ireland Ltd. All rights reserved
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| 8. |
- Flyckt, Lena, et al.
(författare)
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Aberrant tyrosine transport across the fibroblast membrane in patients with schizophrenia : indications of maternal inheritance
- 2011
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Ingår i: Journal of Psychiatric Research. - : Pergamon Press. - 0022-3956 .- 1879-1379. ; 45:4, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- Background: In previous studies of the present patients with schizophrenia, aberrant tyrosine transport across the fibroblast membrane was found. A low K(m), a kinetic factor indicating high affinity between tyrosine and the binding site at the cell membrane, was found to be associated with poor cognitive functions in patients. The present study aimed at investigating possible relationships between patients with schizophrenia and their first-degree relatives in aberrant tyrosine transport indicating that it may be a biological marker for the genetic susceptibility. Methods: Thirty-three parents, 13 fathers and 20 mothers, from 23 families with a schizophrenic patient agreed to enter the study. They underwent skin biopsies for fibroblast cultivation, neuropsychological and psychiatric investigations and were classified as family history positive or negative. Tyrosine transport kinetics (K(m) and V(max)) were calculated from in vitro trials of gradients of extracellular tyrosine concentrations in fibroblast cultures. Results: An association between patients with schizophrenia and their mothers were found for a low K(m) indicating maternal inheritance. Mothers displaying a low K(m) performed worse on the neuropsychological tests compared to mothers with normal K(m). Corresponding relationships between a low K(m) and neurocognitive dysfunction had previously been found for the patients. Conclusions: An aberrant tyrosine transport across plasma membrane may constitute a biological marker for an endophenotype within the schizophrenia spectrum with low cognitive functioning. A plausible mode for genetic transmission is maternal inheritance. (C) 2010 Elsevier Ltd. All rights reserved.
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